NorA, Tet(K), MepA, and MsrA Efflux Pumps in Staphylococcus aureus, their Inhibitors
and 1,8-Naphthyridine Sulfonamides

Cícera   Datiane   de Morais Oliveira-Tintino; Débora   Feitosa   Muniz; Cristina   Rodrigues   dos Santos Barbosa; Raimundo   Luiz   Silva Pereira; Iêda   Maria   Begnini; Ricardo   Andrade   Rebelo; Luiz   Everson   da Silva; Sandro   Lucio   Mireski; Michele   Caroline   Nasato; Maria   Isabel   Lacowicz Krautler; Carlos   Vinicius   Barros Oliveira; Pedro   Silvino   Pereira; Alexandre Magno      Rodrigues Teixeira; Saulo   Relison   Tintino; Irwin Rose   Alencar   de Menezes; Henrique   Douglas   Melo Coutinho; Teresinha   Gonçalves   da Silva
doi:10.2174/1381612829666221212101501
Abstract

Antibiotic resistance can be characterized, in biochemical terms, as an antibiotic’s inability to reach its bacterial target at a concentration that was previously effective. Microbial resistance to different agents can be intrinsic or acquired. Intrinsic resistance occurs due to inherent functional or structural characteristics of the bacteria, such as antibiotic-inactivating enzymes, nonspecific efflux pumps, and permeability barriers. On the other hand, bacteria can acquire resistance mechanisms via horizontal gene transfer in mobile genetic elements such as plasmids. Acquired resistance mechanisms include another category of efflux pumps with more specific substrates, which are plasmid-encoded. Efflux pumps are considered one of the main mechanisms of bacterial resistance to antibiotics and biocides, presenting themselves as integral membrane transporters. They are essential in both bacterial physiology and defense and are responsible for exporting structurally diverse substrates, falling into the following main families: ATP-binding cassette (ABC), multidrug and toxic compound extrusion (MATE), major facilitator superfamily (MFS), small multidrug resistance (SMR) and resistance-nodulation-cell division (RND). The Efflux pumps NorA and Tet(K) of the MFS family, MepA of the MATE family, and MsrA of the ABC family are some examples of specific efflux pumps that act in the extrusion of antibiotics. In this review, we address bacterial efflux pump inhibitors (EPIs), including 1,8-naphthyridine sulfonamide derivatives, given the pre-existing knowledge about the chemical characteristics that favor their biological activity. The modification and emergence of resistance to new EPIs justify further research on this theme, aiming to develop efficient compounds for clinical use.
« Previous Next »
[1]
Cross AS. What Is a Virulence Factor? Crit Care  2008; 12(6): 196.
 [http://dx.doi.org/10.1186/cc7127]

[2]
Martínez JL, Baquero F. Interactions among strategies associated with bacterial infection: Pathogenicity, epidemicity, and antibiotic resistance. Clin Microbiol Rev  2002; 15(4): 647-79.
 [http://dx.doi.org/10.1128/CMR.15.4.647-679.2002]

[3]
Andras JP, Fields PD, Du Pasquier L, Fredericksen M, Ebert D. Genome-wide association analysis identifies a genetic basis of infectivity in a model bacterial pathogen. Mol Biol Evol  2020; 37(12): 3439-52.
 [http://dx.doi.org/10.1093/molbev/msaa173] [PMID: 32658956]

[4]
Morens DM, Folkers GK, Fauci AS. The challenge of emerging and re-emerging infectious diseases. Nature  2004; 430(6996): 242-9.
 [http://dx.doi.org/10.1038/nature02759] [PMID: 15241422]

[5]
Wilson JW, Schurr MJ, LeBlanc CL, Ramamurthy R, Buchanan KL, Nickerson CA. Mechanisms of bacterial pathogenicity. Postgrad Med J  2002; 78(918): 216-24.
 [http://dx.doi.org/10.1136/pmj.78.918.216] [PMID: 11930024]

[6]
Mascaretti OA. Bacterial Pathogenesis.  In: Mascaretti OA, Ed. Bacteria versus Antibacterial Agents American Society for Microbiology (ASM). Washington: USA 2014.

[7]
Fisher RA, Gollan B, Helaine S. Persistent bacterial infections and persister cells. Nat Rev Microbiol  2017; 15(8): 453-64.
 [http://dx.doi.org/10.1038/nrmicro.2017.42] [PMID: 28529326]

[8]
Vogwill T, Comfort AC, Furió V, MacLean RC. Persistence and resistance as complementary bacterial adaptations to antibiotics. J Evol Biol  2016; 29(6): 1223-33.
 [http://dx.doi.org/10.1111/jeb.12864] [PMID: 26999656]

[9]
Ge B, Mukherjee S, Hsu CH, et al. MRSA and multidrug-resistant Staphylococcus aureus in U.S. retail meats, 2010-2011. Food Microbiol  2017; 62: 289-97.
 [http://dx.doi.org/10.1016/j.fm.2016.10.029] [PMID: 27889161]

[10]
Monecke S, Coombs G, Shore AC, et al. A field guide to pandemic, epidemic and sporadic clones of methicillin-resistant Staphylococcus aureus. PLoS One  2011; 6(4): e17936.
 [http://dx.doi.org/10.1371/journal.pone.0017936] [PMID: 21494333]

[11]
Deurenberg R, Stobberingh E. The molecular evolution of hospital- and community-associated methicillin-resistant Staphylococcus au-reus. Curr Mol Med  2009; 9(2): 100-15.
 [http://dx.doi.org/10.2174/156652409787581637] [PMID: 19275621]

[12]
Zhou K, Li C, Chen D, et al. A review on nanosystems as an effective approach against infections of Staphylococcus aureus. Int J Nanomedicine  2018; 13: 7333-47.
 [http://dx.doi.org/10.2147/IJN.S169935] [PMID: 30519018]

[13]
Lima MFP, Borges MA, Parente RS, Júnior RCV, De Oliveira ME. Staphylococcus aureus and hospital infections. Revisão De Literatura  2015; 21(1): 32-9.

[14]
WHO. Publishes list of bacteria for which new antibiotics are urgently needed.  Avaialble from: https://revive.gardp.org/resource/who-priority-pathogens/?cf=encyclopaedia

[15]
Baker S, Thomson N, Weill FX, Holt KE. Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens. Science  2018; 360(6390): 733-8.
 [http://dx.doi.org/10.1126/science.aar3777] [PMID: 29773743]

[16]
Gyles C, Boerlin P. Horizontally transferred genetic elements and their role in pathogenesis of bacterial disease. Vet Pathol  2014; 51(2): 328-40.
 [http://dx.doi.org/10.1177/0300985813511131] [PMID: 24318976]

[17]
Gifford DR, Furió V, Papkou A, Vogwill T, Oliver A, MacLean RC. Identifying and exploiting genes that potentiate the evolution of antibiotic resistance. Nat Ecol Evol  2018; 2(6): 1033-9.
 [http://dx.doi.org/10.1038/s41559-018-0547-x] [PMID: 29686236]

[18]
Blount ZD, Barrick JE, Davidson CJ, Lenski RE. Genomic analysis of a key innovation in an experimental Escherichia coli population. Nature  2012; 489(7417): 513-8.
 [http://dx.doi.org/10.1038/nature11514] [PMID: 22992527]

[19]
Pontes DS, de Araujo RSA, Dantas N, et al. Genetic mechanisms of antibiotic resistance and the role of antibiotic adjuvants. Curr Top Med Chem  2018; 18(1): 42-74.
 [http://dx.doi.org/10.2174/1568026618666180206095224] [PMID: 29412107]

[20]
van Hoek AHAM, Mevius D, Guerra B, Mullany P, Roberts AP, Aarts HJM. Acquired antibiotic resistance genes: An overview. Front Microbiol  2011; 2: 203.
 [http://dx.doi.org/10.3389/fmicb.2011.00203] [PMID: 22046172]

[21]
Miller WR, Munita JM, Arias CA. Mechanisms of antibiotic resistance in enterococci. Expert Rev Anti Infect Ther  2014; 12(10): 1221-36.
 [http://dx.doi.org/10.1586/14787210.2014.956092] [PMID: 25199988]

[22]
Kaatz GW, Seo SM. Inducible NorA-mediated multidrug resistance in Staphylococcus aureus. Antimicrob Agents Chemother  1995; 39(12): 2650-5.
 [http://dx.doi.org/10.1128/AAC.39.12.2650] [PMID: 8592996]

[23]
Lavigne JP, Sotto A, Nicolas-Chanoine MH, Bouziges N, Pagès JM, Davin-Regli A. An adaptive response of Enterobacter aerogenes to imipenem: Regulation of porin balance in clinical isolates. Int J Antimicrob Agents  2013; 41(2): 130-6.
 [http://dx.doi.org/10.1016/j.ijantimicag.2012.10.010] [PMID: 23280442]

[24]
Ubukata K, Itoh-Yamashita N, Konno M. Cloning and expression of the norA gene for fluoroquinolone resistance in Staphylococcus aureus. Antimicrob Agents Chemother  1989; 33(9): 1535-9.
 [http://dx.doi.org/10.1128/AAC.33.9.1535] [PMID: 2817852]

[25]
Guay GG, Khan SA, Rothstein DM. The tet(K) gene of plasmid pT181 of Staphylococcus aureus encodes an efflux protein that contains 14 transmembrane helices. Plasmid  1993; 30(2): 163-6.
 [http://dx.doi.org/10.1006/plas.1993.1045] [PMID: 8234490]

[26]
Kaatz GW, McAleese F, Seo SM. Multidrug resistance in Staphylococcus aureus due to overexpression of a novel multidrug and toxin extrusion (MATE) transport protein. Antimicrob Agents Chemother  2005; 49(5): 1857-64.

[27]
Ross JI, Eady EA, Cove JH, Baumberg S. Identification of a chromosomally encoded ABC-transport system with which the staphylococcal erythromycin exporter MsrA may interact. Gene  1995; 153(1): 93-8.
 [http://dx.doi.org/10.1016/0378-1119(94)00833-E] [PMID: 7883194]

[28]
Poole K. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother  2005; 56(1): 20-51.

[29]
Blair JMA, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJV. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol  2015; 13(1): 42-51.
 [http://dx.doi.org/10.1038/nrmicro3380] [PMID: 25435309]

[30]
Alekshun MN, Levy SB. Molecular mechanisms of antibacterial multidrug resistance. Cell  2007; 128(6): 1037-50.
 [http://dx.doi.org/10.1016/j.cell.2007.03.004] [PMID: 17382878]

[31]
Costa SS, Viveiros M, Amaral L, Couto I. Multidrug efflux pumps in Staphylococcus aureus: An update. Open Microbiol J  2013; 7(1): 59-71.
 [http://dx.doi.org/10.2174/1874285801307010059] [PMID: 23569469]

[32]
Poole K, Lomovskaya O. Can efflux inhibitors really counter resistance? Drug Discov Today Ther Strateg  2006; 3(2): 145-52.
 [http://dx.doi.org/10.1016/j.ddstr.2006.05.005]

[33]
Kapp E, Malan SF, Joubert J, Sampson SL. Small molecule efflux pump inhibitors in Mycobacterium tuberculosis: A rational drug design perspective. Mini Rev Med Chem  2018; 18(1): 72-86.
 [http://dx.doi.org/10.2174/1389557517666170510105506]

[34]
Mahamoud A, Chevalier J, Alibert-Franco S, Kern WV, Pagès JM. Antibiotic efflux pumps in gram-negative bacteria: The inhibitor response strategy. J Antimicrob Chemother  2007; 59(6): 1223-9.
 [http://dx.doi.org/10.1093/jac/dkl493] [PMID: 17229832]

[35]
Wright GD. Resisting resistance: New chemical strategies for battling superbugs. Chem Biol  2000; 7(6): R127-32.
 [http://dx.doi.org/10.1016/S1074-5521(00)00126-5] [PMID: 10873842]

[36]
Monteiro KLC, de Aquino TM, Mendonça Junior FJB. An update on Staphylococcus aureus NorA efflux pump inhibitors. Curr Top Med Chem  2020; 20(24): 2168-85.
 [http://dx.doi.org/10.2174/1568026620666200704135837] [PMID: 32621719]

[37]
Lomovskaya O, Bostian KA. Practical applications and feasibility of efflux pump inhibitors in the clinic - A vision for applied use. Biochem Pharmacol  2006; 71(7): 910-8.
 [http://dx.doi.org/10.1016/j.bcp.2005.12.008] [PMID: 16427026]

[38]
Bell G, MacLean C. The search for ‘Evolution-Proof’ antibiotics. Trends Microbiol  2018; 26(6): 471-83.
 [http://dx.doi.org/10.1016/j.tim.2017.11.005]

[39]
Sommer MOA, Munck C, Toft-Kehler RV, Andersson DI. Prediction of antibiotic resistance: Time for a new preclinical paradigm? Nat Rev Microbiol  2017; 15(11): 689-96.
 [http://dx.doi.org/10.1038/nrmicro.2017.75] [PMID: 28757648]

[40]
Baym M, Stone LK, Kishony R. Multidrug evolutionary strategies to reverse antibiotic resistance. Science  2016; 351(6268): aad3292.
 [http://dx.doi.org/10.1126/science.aad3292] [PMID: 26722002]

[41]
Fernandes P, Martens E. Antibiotics in late clinical development. Biochem Pharmacol  2017; 133: 152-63.
 [http://dx.doi.org/10.1016/j.bcp.2016.09.025] [PMID: 27687641]

[42]
Litvinov VP, Roman S V, Dyachenko VD. Pyridopyridines. Russ Chem Rev  2001; 70: 299-320.

[43]
Litvinov VP. Advances in the chemistry of naphthyridines. Adv Heterocycl Chem  2006; 91: 189-300.
 [http://dx.doi.org/10.1016/S0065-2725(06)91004-6]

[44]
Czuba W. Synthesis and reactions of naphthyridines (review). Chem Heterocycl Compd  1979; 15(1): 1-13.
 [http://dx.doi.org/10.1007/BF00471187]

[45]
Srivastava S, Jha A, Agarwal S, Mukherjee R, Burman A. Synthesis and structure-activity relationships of potent antitumor active quinoline and naphthyridine derivatives. Anticancer Agents Med Chem  2007; 7(6): 685-709.
 [PMID: 18045063]

[46]
Noravyan AS, Paronikyan EG, Vartanyan SA. Synthesis and pharmacological properties of naphthyridines (review). Pharm Chem J  1985; 19(7): 439-48.
 [http://dx.doi.org/10.1007/BF00766678]

[47]
Lesher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP. 1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents. J Med Pharm Chem  1962; 5(5): 1063-5.
 [http://dx.doi.org/10.1021/jm01240a021] [PMID: 14056431]

[48]
Thompson REM, Rae J. NEGRAM (1-ethyI-7-methyl-1, 8-naphthyridine-4-one-3-carboxylic acid): A new antibacterial agent for the treatment of urinary infection report of a trial in general practice. Br J Urol  1964; 36(1): 42-7.
 [http://dx.doi.org/10.1111/j.1464-410X.1964.tb09478.x] [PMID: 14126069]

[49]
Madaan A, Verma R, Kumar V, Singh AT, Jain SK, Jaggi M. 1,8-Naphthyridine derivatives: A review of multiple biological activities. Arch Pharm  2015; 348(12): 837-60.
 [http://dx.doi.org/10.1002/ardp.201500237] [PMID: 26548568]

[50]
Wang H, Wang S, Cheng L, et al. Discovery of Imidazo[1,2-α][1,8]naphthyridine derivatives as potential HCV entry inhibitor. ACS Med Chem Lett  2015; 6(9): 977-81.
 [http://dx.doi.org/10.1021/acsmedchemlett.5b00159] [PMID: 26396683]

[51]
Huang S, Qing J, Wang S, Wang H, Zhang L, Tang Y. Design and synthesis of imidazo[1,2-α][1,8]naphthyridine derivatives as anti-HCV agents via direct C–H arylation. Org Biomol Chem  2014; 12(15): 2344-8.
 [http://dx.doi.org/10.1039/C3OB42525H] [PMID: 24595428]

[52]
Ahmed NS, AlFooty KO, Khalifah SS. Synthesis of 1,8-Naphthyridine derivatives under ultrasound irradiation and cytotoxic activity against HepG2 cell lines. J Chem  2014; 2014: 1-8.
 [http://dx.doi.org/10.1155/2014/126323]

[53]
Roma G, Grossi G, Di Braccio M, et al. 1,8-Naphthyridines VII. New substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides and their isosteric analogues, exhibiting notable anti-inflammatory and/or analgesic activities, but no acute gastrolesivity. Eur J Med Chem  2008; 43(8): 1665-80.
 [http://dx.doi.org/10.1016/j.ejmech.2007.10.010] [PMID: 18045747]

[54]
Kuroda T, Suzuki F, Tamura T, Ohmori K, Hosoe H. A novel synthesis and potent antiinflammatory activity of 4-hydroxy-2(1H)-oxo-1-phenyl-1,8-naphthyridine-3-carboxamides. J Med Chem  1992; 35(6): 1130-6.
 [http://dx.doi.org/10.1021/jm00084a019] [PMID: 1552506]

[55]
Di Braccio M, Grossi G, Alfei S, et al. 1,8-Naphthyridines IX. Potent anti-inflammatory and/or analgesic activity of a new group of substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides, of some their Mannich base derivatives and of one novel substituted 5-amino-10-oxo-10H-pyrimido[1,2-a][1,8]naphthyridine-6-carboxamide derivative. Eur J Med Chem  2014; 86: 394-405.
 [http://dx.doi.org/10.1016/j.ejmech.2014.08.069]

[56]
Madaan A, Kumar V, Verma R, Singh AT, Jain SK, Jaggi M. Anti-inflammatory activity of a naphthyridine derivative (7-chloro-6-fluoro-N-(2-hydroxy-3-oxo-1-phenyl-3-(phenylamino)propyl)-4-oxo-1-(prop-2-yn-1-yl)-1,4-dihydro-1,8-naphthyridine-3-carboxamide) possessing in vitro anticancer potential. Int Immunopharmacol  2013; 15(3): 606-13.
 [http://dx.doi.org/10.1016/j.intimp.2013.01.011] [PMID: 23370301]

[57]
Blum CA, Caldwell T, Zheng X, et al. Discovery of novel 6,6-heterocycles as transient receptor potential vanilloid (TRPV1) antagonists. J Med Chem  2010; 53(8): 3330-48.

[58]
Everson da Silva L, Carlos Joussef A, Kramer Pacheco L, et al. Synthesis and antiparasitic activity against trypanosoma cruzi and leishmania amazonensis of chlorinated 1,7- and 1,8-Naphthyridines. Lett Drug Des Discov  2007; 4(2): 154-9.
 [http://dx.doi.org/10.2174/157018007779422550]

[59]
Domagk G. Chemotherapy in bacterial infections. Angew Chemie 1935.
 [http://dx.doi.org/10.1002/ange.19350484202]

[60]
Bermingham A, Derrick JP. The folic acid biosynthesis pathway in bacteria: Evaluation of potential for antibacterial drug discovery. BioEssays  2002; 24(7): 637-48.
 [http://dx.doi.org/10.1002/bies.10114] [PMID: 12111724]

[61]
Nasr T, Bondock S, Eid S. Design, synthesis, antimicrobial evaluation and molecular docking studies of some new 2,3-dihydrothiazoles and 4-thiazolidinones containing sulfisoxazole. J Enzyme Inhib Med Chem  2016; 31(2): 236-46.
 [http://dx.doi.org/10.3109/14756366.2015.1016514] [PMID: 25815670]

[62]
Holmes NE, Lindsay Grayson M. Sulfonamides Kucers the use of antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs.  (7th Ed.),  2017.

[63]
Holt J, Krieg N, Sneath P, Staley J. Williams S Bergey’s Manual of Determinative Microbiology.  (9th Ed..), Balt.: Lippincot, Williams Wilkins 1994.

[64]
Karl-Heinz Schleifer JAB. Family VIII Staphylococcaceae Fam Nov Bergey’s manual of systematic bacteriology.  (2nd Ed..),  2009.

[65]
Ondusko DS, Nolt D. Staphylococcus aureus. Pediatr Rev  2018; 39(6): 287-98.
 [http://dx.doi.org/10.1542/pir.2017-0224] [PMID: 29858291]

[66]
Parlet CP, Brown MM, Horswill AR. Commensal staphylococci influence Staphylococcus aureus skin colonization and disease. Trends Microbiol  2019; 27(6): 497-507.
 [http://dx.doi.org/10.1016/j.tim.2019.01.008] [PMID: 30846311]

[67]
Kloos WE, Musselwhite MS. Distribution and persistence of Staphylococcus and Micrococcus species and other aerobic bacteria on human skin. Appl Microbiol  1975; 30(3): 381-95.
 [http://dx.doi.org/10.1128/am.30.3.381-395.1975] [PMID: 810086]

[68]
Santos AL, Santos DO, Freitas CC, et al. Staphylococcus aureus: Visiting a strain of hospital importance. J Bras Patol Med Lab  2007; 43(6): 413-23.
 [http://dx.doi.org/10.1590/S1676-24442007000600005]

[69]
Kloos WE, Lambe D. Staphylococcus. In: Ballows A, Hausler WD, Jr, Hermann KL, Isenberg HD, Shadomy HJ, Eds. Manual of Clinical Microbiology.  (5th ed.), Washington, DC: American Society for Microbiology 1991.

[70]
Cassettari VC, Strabelli T, Medeiros EAS. Staphylococcus aureus bacteremia: What is the impact of oxacillin resistance on mortality? Braz J Infect Dis  2005; 9(1): 70-6.
 [http://dx.doi.org/10.1590/S1413-86702005000100012] [PMID: 15947850]

[71]
Trabulsi LR, Alterthum F. Microbiology.  (4th Ed.), Publisher: Atheneu New York 2005.

[72]
Kuroda M, Ohta T, Uchiyama I, et al. Whole genome sequencing of meticillin-resistant Staphylococcus aureus. Lancet  2001; 357(9264): 1225-40.
 [http://dx.doi.org/10.1016/S0140-6736(00)04403-2] [PMID: 11418146]

[73]
Howard JB, Kloos WE. Staphylococci. In: Carson D, Birchor S, Eds. Clinical and Pathogenic Microbiology Missouri. Mosby Co: St Louis 1987.

[74]
Lutz L, Machado A, Kuplich N, Barth AL. Clinical failure of vancomycin treatment of Staphylococcus aureus infection in a tertiary care hospital in southern Brazil. Braz J Infect Dis  2003; 7(3): 224-8.
 [http://dx.doi.org/10.1590/S1413-86702003000300008] [PMID: 14499046]

[75]
Oliveira GA, Okada SS, Guenta RS, Mamizuka EM. Assessment of vancomycin tolerance in 395 nosocomial oxacillin-resistant Staphylococcus aureus strains. J Bras Patol Med Lab  2001; 37(4): 239-46.
 [http://dx.doi.org/10.1590/S1676-24442001000400004]

[76]
Knox KW, Wicken AJ. Immunological properties of teichoic acids. Bacteriol Rev  1973; 37(2): 215-57.
 [http://dx.doi.org/10.1128/br.37.2.215-257.1973] [PMID: 4578758]

[77]
Waldvogel FA. Staphylococcus aureus (Including Toxic Shock Syndrome). In: Mandell GL, Douglas RG, Bennett JE, Eds. Principles and Practice of Infectious Diseases. New York, Edinburgh, London, Melbourne: Churchill Livingstone 1990.

[78]
Koneman EW, et al. Microbiological Diagnosis: Text and Color Atlas.  (6th ed.), Rio de Janeiro: Guanabara Koogan 2008.

[79]
Lowy FD. Staphylococcus aureus Infections. N Engl J Med  1998; 339(8): 520-32.
 [http://dx.doi.org/10.1056/NEJM199808203390806]

[80]
Kahl BC, Becker K, Löffler B. Clinical significance and pathogenesis of staphylococcal small colony variants in persistent infections. Clin Microbiol Rev  2016; 29(2): 401-27.
 [http://dx.doi.org/10.1128/CMR.00069-15] [PMID: 26960941]

[81]
Carvalho CE, Berezin EN, Pistelli IP, Mímica L, Cardoso MRA. Prevalence of Staphylococcus aureus introduced into intensive care units of a university hospital. Braz J Infect Dis  2005; 9(1): 56-63.
 [http://dx.doi.org/10.1590/S0021-75572005000100007]

[82]
Cavalcanti SMM, França ER, Cabral C, et al. Prevalence of Staphylococcus aureus introduced into intensive care units of a university hospital. Braz J Infect Dis  2005; 9(1): 56-63.
 [http://dx.doi.org/10.1590/S1413-86702005000100010] [PMID: 15947848]

[83]
Iaria ST, Furlanetto SM, Campos ML. Staphylococcus aureus research enterotoxigenic in the root handlers food in hospital, São Paulo, 1976. Rev Saude Paul 1980.

[84]
von Eiff C, Becker K, Machka K, Stammer H, Peters G. Nasal carriage as a source of Staphylococcus aureus bacteremia. N Engl J Med  2001; 344(1): 11-6.
 [http://dx.doi.org/10.1056/NEJM200101043440102] [PMID: 11136954]

[85]
Roberts S, Chambers S. Diagnosis and management of Staphylococcus aureus infections of the skin and soft tissue. Intern Med J  2005; 35(s2) (Suppl. 2): S97-S105.
 [http://dx.doi.org/10.1111/j.1444-0903.2005.00983.x] [PMID: 16271065]

[86]
Velazquez-Meza ME. Emergence and spread of methicillinresistant Staphylococcus aureus. Public Health Mex  2005; 47(5): 381-7.
 [http://dx.doi.org/10.1590/S0036-36342005000500009]

[87]
Cluff LE, Reynolds RJ. Management of staphylococcal infections. Am J Med  1965; 39(5): 812-25.
 [http://dx.doi.org/10.1016/0002-9343(65)90100-2] [PMID: 5833577]

[88]
Malanoski GJ, Samore MH, Pefanis A, Karchmer AW. Staphylococcus aureus catheter-associated bacteremia. Minimal effective therapy and unusual infectious complications associated with arterial sheath catheters. Arch Intern Med  1995; 155(11): 1161-6.
 [http://dx.doi.org/10.1001/archinte.1995.00430110069007] [PMID: 7763121]

[89]
Mathew J, Addai T, Anand A, Morrobel A, Maheshwari P, Freels S. Clinical features, site of involvement, bacteriologic findings, and outcome of infective endocarditis in intravenous drug users. Arch Intern Med  1995; 155(15): 1641-8.
 [http://dx.doi.org/10.1001/archinte.1995.00430150125013] [PMID: 7618988]

[90]
Gosbell IB. Diagnosis and management of catheter-related bloodstream infections due to Staphylococcus aureus. Intern Med J  2005; 35(s2) (Suppl. 2): S45-62.
 [http://dx.doi.org/10.1111/j.1444-0903.2005.00979.x] [PMID: 16271061]

[91]
Jacobson MA, Gellermann H, Chambers H. Staphylococcus aureus bacteremia and recurrent staphylococcal infection in patients with acquired immunodeficiency syndrome and aids-related complex. Am J Med  1988; 85(2): 172-6.
 [http://dx.doi.org/10.1016/S0002-9343(88)80337-1] [PMID: 3400693]

[92]
Tong SYC, Davis JS, Eichenberger E, Holland TL, Fowler VG Jr. Staphylococcus aureus infections: Epidemiology, pathophysiology, clinical manifestations, and management. Clin Microbiol Rev  2015; 28(3): 603-61.
 [http://dx.doi.org/10.1128/CMR.00134-14] [PMID: 26016486]

[93]
McGuire E, Boyd A, Woods K. Staphylococcus aureus Bacteremia. Clin Infect Dis  2020; 71(10): 2765-6.
 [http://dx.doi.org/10.1093/cid/ciaa109] [PMID: 32011659]

[94]
Jenul C, Horswill AR. Regulation of Staphylococcus aureus Virulence. Microbiol Spectr  2019; 7(2): 7.2.29.
 [http://dx.doi.org/10.1128/microbiolspec.GPP3-0031-2018] [PMID: 30953424]

[95]
Iwatsuki K, Yamasaki O, Morizane S, Oono T. Staphylococcal cutaneous infections: Invasion, evasion and aggression. J Dermatol Sci  2006; 42(3): 203-14.
 [http://dx.doi.org/10.1016/j.jdermsci.2006.03.011] [PMID: 16679003]

[96]
Weidenmaier C, Kokai-Kun JF, Kristian SA, et al. Role of teichoic acids in Staphylococcus aureus nasal colonization, a major risk factor in nosocomial infections. Nat Med  2004; 10(3): 243-5.
 [http://dx.doi.org/10.1038/nm991] [PMID: 14758355]

[97]
Winstel V, Kühner P, Salomon F, et al. Wall teichoic acid glycosylation governs Staphylococcus aureus nasal colonization. MBio  2015; 6(4): e00632-15.
 [http://dx.doi.org/10.1128/mBio.00632-15] [PMID: 26126851]

[98]
Llewelyn M, Cohen J. Superantigens: Microbial agents that corrupt immunity. Lancet Infect Dis  2002; 2(3): 156-62.
 [http://dx.doi.org/10.1016/S1473-3099(02)00222-0] [PMID: 11944185]

[99]
de Haas CJC, Veldkamp KE, Peschel A, et al. Chemotaxis inhibitory protein of Staphylococcus aureus, a bacterial antiinflammatory agent. J Exp Med  2004; 199(5): 687-95.
 [http://dx.doi.org/10.1084/jem.20031636] [PMID: 14993252]

[100]
Chavakis T, Hussain M, Kanse SM, et al. Staphylococcus aureus extracellular adherence protein serves as anti-inflammatory factor by inhibiting the recruitment of host leukocytes. Nat Med  2002; 8(7): 687-93.
 [http://dx.doi.org/10.1038/nm728] [PMID: 12091905]

[101]
Gresham HD, Lowrance JH, Caver TE, Wilson BS, Cheung AL, Lindberg FP. Survival of Staphylococcus aureus inside neutrophils contributes to infection. J Immunol  2000; 164(7): 3713-22.
 [http://dx.doi.org/10.4049/jimmunol.164.7.3713] [PMID: 10725730]

[102]
Lee LY, Miyamoto YJ, McIntyre BW, et al. The Staphylococcus aureus Map protein is an immunomodulator that interferes with T cell-mediated responses. J Clin Invest  2002; 110(10): 1461-71.
 [http://dx.doi.org/10.1172/JCI0216318] [PMID: 12438444]

[103]
Foster TJ, McDevitt D. Surface-associated proteins of Staphylococcus aureus: Their possible roles in virulence. FEMS Microbiol Lett  1994; 118(3): 199-205.
 [http://dx.doi.org/10.1111/j.1574-6968.1994.tb06828.x] [PMID: 8020742]

[104]
Foster TJ. Immune evasion by staphylococci. Nat Rev Microbiol  2005; 3(12): 948-58.
 [http://dx.doi.org/10.1038/nrmicro1289] [PMID: 16322743]

[105]
Fedtke I, Götz F, Peschel A. Bacterial evasion of innate host defenses-the Staphylococcus aureus lesson. Int J Med Microbiol  2004; 294(2-3): 189-94.
 [http://dx.doi.org/10.1016/j.ijmm.2004.06.016] [PMID: 15493829]

[106]
Flannagan R, Heit B, Heinrichs D. Antimicrobial mechanisms of macrophages and the immune evasion strategies of Staphylococcus aureus. Pathogens  2015; 4(4): 826-68.
 [http://dx.doi.org/10.3390/pathogens4040826] [PMID: 26633519]

[107]
Grumann D, Nübel U, Bröker BM. Staphylococcus aureus toxins-Their functions and genetics. Infect Genet Evol  2014; 21: 583-92.
 [http://dx.doi.org/10.1016/j.meegid.2013.03.013] [PMID: 23541411]

[108]
Dinges MM, Orwin PM, Schlievert PM. Exotoxins of Staphylococcus aureus. Clin Microbiol Rev  2000; 13(1): 16-34.
 [http://dx.doi.org/10.1128/CMR.13.1.16] [PMID: 10627489]

[109]
Bush K, Jacoby GA. Updated functional classification of β-lactamases. Antimicrob Agents Chemother  2010; 54(3): 969-76.
 [http://dx.doi.org/10.1128/AAC.01009-09] [PMID: 19995920]

[110]
Chang J, Lee RE, Lee W. A pursuit of Staphylococcus aureus continues: A role of persister cells. Arch Pharm Res  2020; 43(6): 630-8.
 [http://dx.doi.org/10.1007/s12272-020-01246-x] [PMID: 32627141]

[111]
Lee AS, De Lencastre H, Garau J, et al. Methicillin-resistant Staphylococcus aureus. Nat Rev Dis Prim  2018; 4: 18033.
 [http://dx.doi.org/10.1038/nrdp.2018.33]

[112]
Stryjewski ME, Corey GR. Methicillin-resistant Staphylococcus aureus: An evolving pathogen. Clin Infect Dis  2014; 58 (Suppl. 1): S10-9.
 [http://dx.doi.org/10.1093/cid/cit613] [PMID: 24343827]

[113]
Turner NA, Sharma-Kuinkel BK, Maskarinec SA, et al. Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research. Nat Rev Microbiol  2019; 17(4): 203-18.
 [http://dx.doi.org/10.1038/s41579-018-0147-4] [PMID: 30737488]

[114]
Marshall BM, Levy SB. Food animals and antimicrobials: Impacts on human health. Clin Microbiol Rev  2011; 24(4): 718-33.
 [http://dx.doi.org/10.1128/CMR.00002-11] [PMID: 21976606]

[115]
Wright GD. Antibiotic resistance in the environment: A link to the clinic? Curr Opin Microbiol  2010; 13(5): 589-94.
 [http://dx.doi.org/10.1016/j.mib.2010.08.005] [PMID: 20850375]

[116]
D’Costa VM, Griffiths E, Wright GD. Expanding the soil antibiotic resistome: Exploring environmental diversity. Curr Opin Microbiol  2007; 10(5): 481-9.
 [http://dx.doi.org/10.1016/j.mib.2007.08.009] [PMID: 17951101]

[117]
Aminov RI, Mackie RI. Evolution and ecology of antibiotic resistance genes. FEMS Microbiol Lett  2007; 271(2): 147-61.
 [http://dx.doi.org/10.1111/j.1574-6968.2007.00757.x] [PMID: 17490428]

[118]
Silbergeld EK, Graham J, Price LB. Industrial food animal production, antimicrobial resistance, and human health. Annual Review of Public Health.  2008.

[119]
Alcock BP, Raphenya AR, Lau TTY, et al. CARD 2020: Antibiotic resistome surveillance with the comprehensive antibiotic resistance database. Nucleic Acids Res  2020; 48(D1): D517-25.
 [PMID: 31665441]

[120]
Fajardo A, Martínez-Martín N, Mercadillo M, et al. The neglected intrinsic resistome of bacterial pathogens. PLoS One  2008; 3(2): e1619.
 [http://dx.doi.org/10.1371/journal.pone.0001619] [PMID: 18286176]

[121]
Cox G, Wright GD. Intrinsic antibiotic resistance: Mechanisms, origins, challenges and solutions. Int J Med Microbiol  2013; 303(6-7): 287-92.
 [http://dx.doi.org/10.1016/j.ijmm.2013.02.009] [PMID: 23499305]

[122]
Wright GD. The antibiotic resistome: The nexus of chemical and genetic diversity. Nat Rev Microbiol  2007; 5(3): 175-86.
 [http://dx.doi.org/10.1038/nrmicro1614] [PMID: 17277795]

[123]
Dantas G, Sommer MOA. Context matters-the complex interplay between resistome genotypes and resistance phenotypes. Curr Opin Microbiol  2012; 15(5): 577-82.
 [http://dx.doi.org/10.1016/j.mib.2012.07.004] [PMID: 22954750]

[124]
Martínez JL. Ecology and evolution of chromosomal gene transfer between environmental microorganisms and pathogens. Microbiol Spectr  2018; 6(1): 6.1.06.
 [http://dx.doi.org/10.1128/microbiolspec.MTBP-0006-2016] [PMID: 29350130]

[125]
Peterson E, Kaur P. Antibiotic resistance mechanisms in bacteria: Relationships between resistance determinants of antibiotic producers, environmental bacteria, and clinical pathogens. Front Microbiol  2018; 9: 2928.
 [http://dx.doi.org/10.3389/fmicb.2018.02928] [PMID: 30555448]

[126]
Wright GD. Molecular mechanisms of antibiotic resistance. Chem Commun (Camb)  2011; 47(14): 4055-61.
 [http://dx.doi.org/10.1039/c0cc05111j] [PMID: 21286630]

[127]
Fishovitz J, Hermoso JA, Chang M, Mobashery S. Penicillin-binding protein 2a of methicillin-resistant Staphylococcus aureus. IUBMB Life  2014; 66(8): 572-7.
 [http://dx.doi.org/10.1002/iub.1289] [PMID: 25044998]

[128]
Liu J, Chen D, Peters BM, et al. Staphylococcal chromosomal cassettes mec (SCCmec): A mobile genetic element in methicillin-resistant Staphylococcus aureus. Microb Pathog  2016; 101: 56-67.
 [http://dx.doi.org/10.1016/j.micpath.2016.10.028] [PMID: 27836760]

[129]
Katayama Y, Ito T, Hiramatsu K. A new class of genetic element, staphylococcus cassette chromosome mec, encodes methicillin resistance in Staphylococcus aureus. Antimicrob Agents Chemother  2000; 44(6): 1549-55.

[130]
Kumar N, Radhakrishnan A, Wright CC, et al. Crystal structure of the transcriptional regulator Rv1219c of Mycobacterium tuberculosis. Protein Sci  2014; 23(4): 423-32.
 [http://dx.doi.org/10.1002/pro.2424] [PMID: 24424575]

[131]
Vester B, Douthwaite S. Macrolide resistance conferred by base substitutions in 23S rRNA. Antimicrob Agents Chemother  2001; 45(1): 1-12.
 [http://dx.doi.org/10.1128/AAC.45.1.1-12.2001] [PMID: 11120937]

[132]
Weisblum B. Erythromycin resistance by ribosome modification. Antimicrob Agents Chemother  1995; 39(3): 577-85.
 [http://dx.doi.org/10.1128/AAC.39.3.577] [PMID: 7793855]

[133]
Long KS, Poehlsgaard J, Kehrenberg C, Schwarz S, Vester B. The Cfr rRNA methyltransferase confers resistance to phenicols, lincosamides, oxazolidinones, pleuromutilins, and streptogramin A antibiotics. Antimicrob Agents Chemother  2006; 50(7): 2500-5.
 [http://dx.doi.org/10.1128/AAC.00131-06] [PMID: 16801432]

[134]
Roberts MC, Sutcliffe J, Courvalin P, Jensen LB, Rood J, Seppala H. Nomenclature for macrolide and macrolide-lincosamide-streptogramin B resistance determinants. Antimicrob Agents Chemother  1999; 43(12): 2823-30.
 [http://dx.doi.org/10.1128/AAC.43.12.2823] [PMID: 10582867]

[135]
Kehrenberg C, Schwarz S, Jacobsen L, Hansen LH, Vester B. A new mechanism for chloramphenicol, florfenicol and clindamycin re-sistance: Methylation of 23S ribosomal RNA at A2503. Mol Microbiol  2005; 57(4): 1064-73.
 [http://dx.doi.org/10.1111/j.1365-2958.2005.04754.x] [PMID: 16091044]

[136]
Binda E, Marinelli F, Marcone G. Old and new glycopeptide antibiotics: Action and resistance. Antibiotics  2014; 3(4): 572-94.
 [http://dx.doi.org/10.3390/antibiotics3040572] [PMID: 27025757]

[137]
Bugg TDH, Wright GD, Dutka-Malen S, Arthur M, Courvalin P, Walsh CT. Molecular basis for vancomycin resistance in Enterococcus faecium BM4147: Biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry  1991; 30(43): 10408-15.
 [http://dx.doi.org/10.1021/bi00107a007] [PMID: 1931965]

[138]
Billot-Klein D, Blanot D, Gutmann L, van Heijenoort J. Association constants for the binding of vancomycin and teicoplanin to N-acetyl-d-alanyl-d-alanine and N-acetyl-d-alanyl-d-serine. Biochem J  1994; 304(3): 1021-2.
 [http://dx.doi.org/10.1042/bj3041021] [PMID: 7818465]

[139]
Vetting MW, Hegde SS, Wang M, Jacoby GA, Hooper DC, Blanchard JS. Structure of QnrB1, a plasmid-mediated fluoroquinolone resistance factor. J Biol Chem  2011; 286(28): 25265-73.
 [http://dx.doi.org/10.1074/jbc.M111.226936] [PMID: 21597116]

[140]
Shakil S, Khan R, Zarrilli R, Khan AU. Aminoglycosides versus bacteria - a description of the action, resistance mechanism, and nosocomial battleground. J Biomed Sci  2008; 15(1): 5-14.
 [http://dx.doi.org/10.1007/s11373-007-9194-y] [PMID: 17657587]

[141]
Fritsche TR, Castanheira M, Miller GH, Jones RN, Armstrong ES. Detection of methyltransferases conferring high-level resistance to aminoglycosides in enterobacteriaceae from Europe, North America, and Latin America. Antimicrob Agents Chemother  2008; 52(5): 1843-5.

[142]
Hidalgo L, Hopkins KL, Gutierrez B, et al. Association of the novel aminoglycoside resistance determinant RmtF with NDM carbapenemase in Enterobacteriaceae isolated in India and the UK. J Antimicrob Chemother  2013; 68(7): 1543-50.
 [http://dx.doi.org/10.1093/jac/dkt078] [PMID: 23580560]

[143]
Savic M, Lovrić J, Tomic TI, Vasiljevic B, Conn GL. Determination of the target nucleosides for members of two families of 16S rRNA methyltransferases that confer resistance to partially overlapping groups of aminoglycoside antibiotics. Nucleic Acids Res  2009; 37(16): 5420-31.
 [http://dx.doi.org/10.1093/nar/gkp575] [PMID: 19589804]

[144]
Blanco MG, Hardisson C, Salas JA. Resistance in inhibitors of RNA polymerase in actinomycetes which produce them. J Gen Microbiol  1984; 130(11): 2883-91.
 [PMID: 6084703]

[145]
Abraham EP, Chain E. An Enzyme from Bacteria able to Destroy Penicillin. Nature  1940; 146(3713): 837.
 [http://dx.doi.org/10.1038/146837a0]

[146]
Johnson AP, Woodford N. Global spread of antibiotic resistance: The example of New Delhi metallo-β-lactamase (NDM)-mediated carbapenem resistance. J Med Microbiol  2013; 62(4): 499-513.
 [http://dx.doi.org/10.1099/jmm.0.052555-0] [PMID: 23329317]

[147]
Lynch JP III, Clark NM, Zhanel GG. Evolution of antimicrobial resistance among Enterobacteriaceae (focus on extended spectrum β-lactamases and carbapenemases). Expert Opin Pharmacother  2013; 14(2): 199-210.
 [http://dx.doi.org/10.1517/14656566.2013.763030] [PMID: 23321047]

[148]
Jacoby GA. AmpC β-Lactamases. Clin Microbiol Rev  2009; 22(1): 161-82.
 [http://dx.doi.org/10.1128/CMR.00036-08]

[149]
Wiedemann B, Pfeifle D, Wiegand I, Janas E. β-Lactamase induction and cell wall recycling in gram-negative bacteria. Drug Resist Updat  1998; 1(4): 223-6.
 [http://dx.doi.org/10.1016/S1368-7646(98)80002-2] [PMID: 16904404]

[150]
Wright G. Bacterial resistance to antibiotics: Enzymatic degradation and modification. Adv Drug Deliv Rev  2005; 57(10): 1451-70.
 [http://dx.doi.org/10.1016/j.addr.2005.04.002] [PMID: 15950313]

[151]
Norris AL, Serpersu EH. Ligand promiscuity through the eyes of the aminoglycoside N 3 acetyltransferase IIa. Protein Sci  2013; 22(7): 916-28.
 [http://dx.doi.org/10.1002/pro.2273] [PMID: 23640799]

[152]
Ramirez MS, Tolmasky ME. Aminoglycoside modifying enzymes. Drug Resist Updat  2010; 13(6): 151-71.
 [http://dx.doi.org/10.1016/j.drup.2010.08.003] [PMID: 20833577]

[153]
Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev  2003; 67(4): 593-656.
 [http://dx.doi.org/10.1128/MMBR.67.4.593-656.2003] [PMID: 14665678]

[154]
Choi HJ, Kim DW, Choi YW, et al. Broad-spectrum In vitro antimicrobial activities of Streptomyces sp. strain BCNU 1001. Biotechnol Bioproc E1  2012; 7(3): 576-83.
 [http://dx.doi.org/10.1007/s12257-011-0151-2]

[155]
Kojima S, Nikaido H. Permeation rates of penicillins indicate that Escherichia coli porins function principally as nonspecific channels. Proc Natl Acad Sci USA  2013; 110(28): E2629-34.
 [http://dx.doi.org/10.1073/pnas.1310333110]

[156]
Li H, Luo YF, Williams BJ, Blackwell TS, Xie CM. Structure and function of OprD protein in Pseudomonas aeruginosa: From antibiotic resistance to novel therapies. Int J Med Microbiol  2012; 302(2): 63-8.
 [http://dx.doi.org/10.1016/j.ijmm.2011.10.001] [PMID: 22226846]

[157]
Hancock REW, Hancock REW. On the mechanism of solute uptake in Pseudomonas. Front Biosci  2003; 8(6): 1075.
 [http://dx.doi.org/10.2741/1075] [PMID: 12700103]

[158]
Tängdén T, Adler M, Cars O, Sandegren L, Löwdin E. Frequent emergence of porin-deficient subpopulations with reduced carbapenem susceptibility in ESBL-producing Escherichia coli during exposure to ertapenem in an in vitro pharmacokinetic model. J Antimicrob Chemother  2013; 68(6): 1319-26.
 [http://dx.doi.org/10.1093/jac/dkt044] [PMID: 23478794]

[159]
Novais Â, Rodrigues C, Branquinho R, et al. Spread of an OmpK36-modified ST15 Klebsiella pneumoniae variant during an outbreak involving multiple carbapenem-resistant Enterobacteriaceae species and clones. Eur J Clin Microbiol Infect Dis  2012; 31(11): 3057-63.
 [http://dx.doi.org/10.1007/s10096-012-1665-z] [PMID: 22706513]

[160]
Nikaido H, Takatsuka Y. Mechanisms of RND multidrug efflux pumps. Biochim Biophys Acta Proteins Proteomics  2009; 1794(5): 769-81.
 [http://dx.doi.org/10.1016/j.bbapap.2008.10.004] [PMID: 19026770]

[161]
Roberts MC. Update on acquired tetracycline resistance genes. FEMS Microbiol Lett  2005; 245(2): 195-203.
 [http://dx.doi.org/10.1016/j.femsle.2005.02.034] [PMID: 15837373]

[162]
Bismuth R, Zilhao R, Sakamoto H, Guesdon JL, Courvalin P. Gene heterogeneity for tetracycline resistance in Staphylococcus spp. Antimicrob Agents Chemother  1990; 34(8): 1611-4.
 [http://dx.doi.org/10.1128/AAC.34.8.1611] [PMID: 2221873]

[163]
Lee A, Mao W, Warren MS, et al. Interplay between efflux pumps may provide either additive or multiplicative effects on drug resistance. J Bacteriol  2000; 182(11): 3142-50.
 [http://dx.doi.org/10.1128/JB.182.11.3142-3150.2000] [PMID: 10809693]

[164]
Kaatz GW, Thyagarajan RV, Seo SM. Effect of promoter region mutations and mgrA overexpression on transcription of norA, which encodes a Staphylococcus aureus multidrug efflux transporter. Antimicrob Agents Chemother  2005; 49(1): 161-9.
 [http://dx.doi.org/10.1128/AAC.49.1.161-169.2005] [PMID: 15616291]

[165]
Warner DM, Shafer WM, Jerse AE. Clinically relevant mutations that cause derepression of the Neisseria gonorrhoeae MtrC-MtrDMtrE Efflux pump system confer different levels of antimicrobial resistance and in vivo fitness. Mol Microbiol  2008; 70(2): 462-78.
 [http://dx.doi.org/10.1111/j.1365-2958.2008.06424.x] [PMID: 18761689]

[166]
Olliver A, Vallé M, Chaslus-Dancla E, Cloeckaert A. Role of an acrR mutation in multidrug resistance of in vitro-selected fluoroquinolone-resistant mutants of Salmonella enterica serovar Typhimurium. FEMS Microbiol Lett  2004; 238(1): 267-72.
 [PMID: 15336432]

[167]
Webber MA, Piddock LJV. Absence of mutations in marRAB or soxRS in acrB-overexpressing fluoroquinolone-resistant clinical and veterinary isolates of Escherichia coli. Antimicrob Agents Chemother  2001; 45(5): 1550-2.
 [http://dx.doi.org/10.1128/AAC.45.5.1550-1552.2001] [PMID: 11302826]

[168]
Wang K, Pei H, Huang B, et al. The expression of ABC efflux pump, Rv1217c-Rv1218c, and its association with multidrug resistance of Mycobacterium tuberculosis in China. Curr Microbiol  2013; 66(3): 222-6.
 [http://dx.doi.org/10.1007/s00284-012-0215-3] [PMID: 23143285]

[169]
Yamasaki S, Nikaido E, Nakashima R, et al. The crystal structure of multidrug-resistance regulator RamR with multiple drugs. Nat Commun  2013; 4(1): 2078.
 [http://dx.doi.org/10.1038/ncomms3078] [PMID: 23800819]

[170]
Zalucki YM, Dhulipala V, Shafer WM. Dueling regulatory properties of a transcriptional activator (MtrA) and repressor (MtrR) that con-trol efflux pump gene expression in Neisseria gonorrhoeae. MBio  2012; 3(6): e00446-12.
 [http://dx.doi.org/10.1128/mBio.00446-12] [PMID: 23221802]

[171]
Baucheron S, Nishino K, Monchaux I, et al. Bile-mediated activation of the acrAB and tolC multidrug efflux genes occurs mainly through transcriptional derepression of ramA in Salmonella enterica serovar Typhimurium. J Antimicrob Chemother  2014; 69(9): 2400-6.
 [http://dx.doi.org/10.1093/jac/dku140] [PMID: 24816212]

[172]
Hirakawa H, Inazumi Y, Masaki T, Hirata T, Yamaguchi A. Indole induces the expression of multidrug exporter genes in Escherichia coli. Mol Microbiol  2005; 55(4): 1113-26.
 [http://dx.doi.org/10.1111/j.1365-2958.2004.04449.x] [PMID: 15686558]

[173]
Nikaido E, Giraud E, Baucheron S, et al. Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses. Gut Pathog  2012; 4(1): 5.
 [http://dx.doi.org/10.1186/1757-4749-4-5] [PMID: 22632036]

[174]
Nikaido E, Shirosaka I, Yamaguchi A, Nishino K. Regulation of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium in response to indole and paraquat. Microbiology (Reading)  2011; 157(3): 648-55.
 [http://dx.doi.org/10.1099/mic.0.045757-0] [PMID: 21148208]

[175]
Levy SB. Active efflux mechanisms for antimicrobial resistance. Antimicrob Agents Chemother  1992; 36(4): 695-703.
 [http://dx.doi.org/10.1128/AAC.36.4.695] [PMID: 1503431]

[176]
Sun J, Deng Z, Yan A. Bacterial multidrug efflux pumps: Mechanisms, physiology and pharmacological exploitations. Biochem Biophys Res Commun  2014; 453(2): 254-67.
 [http://dx.doi.org/10.1016/j.bbrc.2014.05.090] [PMID: 24878531]

[177]
McMurry L, Petrucci RE, Levy SB. Active efflux of tetracycline encoded by four genetically different tetracyline resistance determinants in Escherichia coli. Proc Natl Acad Sci USA  1980; 77(7): 3974-7.

[178]
Benveniste R, Davies J. Aminoglycoside antibiotic inactivating enzymes in actinomycetes similar to those present in clinical isolates of antibiotic resistant bacteria. Proc Natl Acad Sci USA 1973.
 [http://dx.doi.org/10.1073/pnas.70.8.2276]

[179]
Davies J. Inactivation of antibiotics and the dissemination of resistance genes. Science  1994; 264(5157): 375-82.
 [http://dx.doi.org/10.1126/science.8153624]

[180]
Martínez-Suárez JV, Martínez JL, Goicoechea MJLD, et al. Acquisition of antibiotic resistance plasmids in vivo by extraintestinal Salmonella spp. J Antimicrob Chemother  1987; 20(3): 452-3.
 [http://dx.doi.org/10.1093/jac/20.3.452] [PMID: 3680083]

[181]
Martinez JL, Fajardo A, Garmendia L, et al. A global view of antibiotic resistance. FEMS Microbiol Rev  2009; 33(1): 44-65.
 [http://dx.doi.org/10.1111/j.1574-6976.2008.00142.x] [PMID: 19054120]

[182]
Martinez JL, Sánchez MB, Martínez-Solano L, et al. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol Rev  2009; 33(2): 430-49.
 [http://dx.doi.org/10.1111/j.1574-6976.2008.00157.x] [PMID: 19207745]

[183]
Van Bambeke F, Balzi E, Tulkens PM. Antibiotic efflux pumps. Biochem Pharmacol  2000; 60(4): 457-70.
 [http://dx.doi.org/10.1016/S0006-2952(00)00291-4] [PMID: 10874120]

[184]
Webber MA, Piddock LJV. The importance of efflux pumps in bacterial antibiotic resistance. J Antimicrob Chemother  2003; 51(1): 9-11.
 [http://dx.doi.org/10.1093/jac/dkg050] [PMID: 12493781]

[185]
Nikaido H. Multidrug resistance in bacteria. Annu Rev Biochem  2009; 78(1): 119-46.
 [http://dx.doi.org/10.1146/annurev.biochem.78.082907.145923] [PMID: 19231985]

[186]
Cannon RD, Lamping E, Holmes AR, et al. Efflux-mediated antifungal drug resistance. Clin Microbiol Rev  2009; 22(2): 291-321.
 [http://dx.doi.org/10.1128/CMR.00051-08] [PMID: 19366916]

[187]
Van Bambeke F, Michot JM, Tulkens PM. Antibiotic efflux pumps in eukaryotic cells: Occurrence and impact on antibiotic cellular pharmacokinetics, pharmacodynamics and toxicodynamics. J Antimicrob Chemother  2003; 51(5): 1067-77.
 [http://dx.doi.org/10.1093/jac/dkg225]

[188]
Babiker HA, Pringle SJ, Abdel-Muhsin A, Mackinnon M, Hunt P, Walliker D. High-level chloroquine resistance in Sudanese isolates of Plasmodium falciparum is associated with mutations in the chloroquine resistance transporter gene pfcrt and the multidrug resistance Gene pfmdr1. J Infect Dis  2001; 183(10): 1535-8.
 [http://dx.doi.org/10.1086/320195] [PMID: 11319692]

[189]
Harbottle H, Thakur S, Zhao S, White DG. Genetics of antimicrobial resistance. Anim Biotechnol  2006; 17(2): 111-24.
 [http://dx.doi.org/10.1080/10495390600957092] [PMID: 17127523]

[190]
Kumar S, Lindquist IE, Sundararajan A, et al. Genome Sequence of Non-O1 Vibrio Cholerae PS15. Genome Announc  2013; 1(1): e00227-12.
 [http://dx.doi.org/10.1128/genomeA.00227-12] [PMID: 23409261]

[191]
Biswas S, Raoult D, Rolain JM. A bioinformatic approach to understanding antibiotic resistance in intracellular bacteria through whole genome analysis. Int J Antimicrob Agents  2008; 32(3): 207-20.
 [http://dx.doi.org/10.1016/j.ijantimicag.2008.03.017]

[192]
Wright GD. The antibiotic resistome. Expert Opin Drug Discov  2010; 5(8): 779-88.
 [http://dx.doi.org/10.1517/17460441.2010.497535] [PMID: 22827799]

[193]
Baysarowich J, Koteva K, Hughes DW, et al. Rifamycin antibiotic resistance by adp-ribosylation: Structure and diversity of arr. Proc Natl Acad Sci USA  2008; 105(12): 4886-91.

[194]
Nichols RJ, Sen S, Choo YJ, et al. Phenotypic landscape of a bacterial cell. Cell  2011; 144(1): 143-56.
 [http://dx.doi.org/10.1016/j.cell.2010.11.052] [PMID: 21185072]

[195]
Tal N, Schuldiner S. A coordinated network of transporters with overlapping specificities provides a robust survival strategy. Proc Natl Acad Sci USA  2009; 106(22): 9051-6.
 [http://dx.doi.org/10.1073/pnas.0902400106]

[196]
Poole K, Srikumar R. Multidrug efflux in Pseudomonas aeruginosa components, mechanisms and clinical significance. Curr Top Med Chem 2005.
 [PMID: 11895293]

[197]
Rahman T, Yarnall B, Doyle DA. Efflux drug transporters at the forefront of antimicrobial resistance. Eur Biophys J  2017; 46(7): 647-53.
 [http://dx.doi.org/10.1007/s00249-017-1238-2] [PMID: 28710521]

[198]
Gandra S, Alvarez-Uria G, Turner P, Joshi J, Limmathurotsakul D, van Doorn HR. Antimicrobial resistance surveillance in low- and middle-income countries: Progress and challenges in eight South Asian and Southeast Asian countries. Clin Microbiol Rev  2020; 33(3): e00048-19.
 [http://dx.doi.org/10.1128/CMR.00048-19] [PMID: 32522747]

[199]
Chuanchuen R, Beinlich K, Hoang TT, Becher A, Karkhoff-Schweizer RR, Schweizer HP. Cross-resistance between triclosan and antibiotics in Pseudomonas aeruginosa is mediated by multidrug efflux pumps: Exposure of a susceptible mutant strain to triclosan selects nfxB mutants overexpressing MexCD-OprJ. Antimicrob Agents Chemother  2001; 45(2): 428-32.
 [http://dx.doi.org/10.1128/AAC.45.2.428-432.2001] [PMID: 11158736]

[200]
Nakae T, Nakajima A, Ono T, Saito K, Yoneyama H. Resistance to β-lactam antibiotics in Pseudomonas aeruginosa due to interplay between the MexAB-OprM efflux pump and β-lactamase. Antimicrob Agents Chemother  1999; 43(5): 1301-3.
 [http://dx.doi.org/10.1128/AAC.43.5.1301] [PMID: 10223959]

[201]
Nakajima A, Sugimoto Y, Yoneyama H, Nakae T. High-level fluoroquinolone resistance in Pseudomonas aeruginosa due to interplay of the MexAB-OprM efflux pump and the DNA gyrase mutation. Microbiol Immunol  2002; 46(6): 391-5.
 [http://dx.doi.org/10.1111/j.1348-0421.2002.tb02711.x] [PMID: 12153116]

[202]
Hirai K, Suzue S, Irikura T, Iyobe S, Mitsuhashi S. Mutations producing resistance to norfloxacin in Pseudomonas aeruginosa. Antimicrob Agents Chemother  1987; 31(4): 582-6.
 [http://dx.doi.org/10.1128/AAC.31.4.582] [PMID: 3111356]

[203]
Martinez JL. The role of natural environments in the evolution of resistance traits in pathogenic bacteria. Proc Biol Sci  2009; 276(1667): 2521-30.
 [http://dx.doi.org/10.1098/rspb.2009.0320]

[204]
Alvarez-Ortega C, Olivares J, Martínez JL. RND multidrug efflux pumps: What are they good for? Front Microbiol  2013; 4: 7.
 [http://dx.doi.org/10.3389/fmicb.2013.00007] [PMID: 23386844]

[205]
Nies DH. Efflux-mediated heavy metal resistance in prokaryotes. FEMS Microbiol Rev  2003; 27(2-3): 313-39.
 [http://dx.doi.org/10.1016/S0168-6445(03)00048-2] [PMID: 12829273]

[206]
Zgurskaya HI, Nikaido H. Multidrug resistance mechanisms: Drug efflux across two membranes. Mol Microbiol  2000; 37(2): 219-25.
 [http://dx.doi.org/10.1046/j.1365-2958.2000.01926.x] [PMID: 10931319]

[207]
Ramos JL, Duque E, Gallegos MT, et al. Mechanisms of solvent tolerance in gram-negative bacteria. Annu Rev Microbiol  2002; 56(1): 743-68.
 [http://dx.doi.org/10.1146/annurev.micro.56.012302.161038] [PMID: 12142492]

[208]
Lin J, Sahin O, Michel LO, Zhang Q. Critical role of multidrug efflux pump CmeABC in bile resistance and in vivo colonization of Campylobacter jejuni. Infect Immun  2003; 71(8): 4250-9.
 [http://dx.doi.org/10.1128/IAI.71.8.4250-4259.2003] [PMID: 12874300]

[209]
Bina JE, Mekalanos JJ. Vibrio Cholerae tolC is required for bile resistance and colonization. Infect Immun  2001; 69(7): 4681-5.
 [http://dx.doi.org/10.1128/IAI.69.7.4681-4685.2001] [PMID: 11402016]

[210]
Prouty AM, Brodsky IE, Falkow S, Gunn JS. Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella typhimurium. Microbiology  2004; 150(4): 775-83.
 [http://dx.doi.org/10.1099/mic.0.26769-0] [PMID: 15073288]

[211]
Lacroix FJC, Cloeckaert A, Grépinet O, et al. Salmonella typhimurium acrB-like gene: Identification and role in resistance to biliary salts and detergents and in murine infection. FEMS Microbiol Lett  1996; 135(2-3): 161-7.
 [http://dx.doi.org/10.1111/j.1574-6968.1996.tb07983.x] [PMID: 8595853]

[212]
Koronakis V, Eswaran J, Hughes C. Structure and function of TolC: The bacterial exit duct for proteins and drugs. Annu Rev Biochem  2004; 73: 467-89.

[213]
Elkins CA, Mullis LB. Mammalian steroid hormones are substrates for the major RND- and MFS-type tripartite multidrug efflux pumps of Escherichia coli. J Bacteriol  2006; 188(3): 1191-5.
 [http://dx.doi.org/10.1128/JB.188.3.1191-1195.2006] [PMID: 16428427]

[214]
Burse A, Weingart H, Ullrich MS. The phytoalexin-inducible multidrug efflux pump AcrAB contributes to virulence in the fire blight pathogen, Erwinia amylovora. Mol Plant Microbe Interact  2004; 17(1): 43-54.
 [http://dx.doi.org/10.1094/MPMI.2004.17.1.43] [PMID: 14714867]

[215]
Nishino K, Latifi T, Groisman EA. Virulence and drug resistance roles of multidrug efflux systems of Salmonella enterica serovar Typhimurium. Mol Microbiol  2006; 59(1): 126-41.
 [http://dx.doi.org/10.1111/j.1365-2958.2005.04940.x] [PMID: 16359323]

[216]
Stone BJ, Miller VL. Salmonella enteritidis has a homologue of tolC that is required for virulence in BALB/c mice. Mol Microbiol  1995; 17(4): 701-12.
 [http://dx.doi.org/10.1111/j.1365-2958.1995.mmi_17040701.x] [PMID: 8801424]

[217]
Buckley AM, Webber MA, Cooles S, et al. The AcrAB-TolC efflux system of Salmonella enterica serovar Typhimurium plays a role in pathogenesis. Cell Microbiol  2006; 8(5): 847-56.
 [http://dx.doi.org/10.1111/j.1462-5822.2005.00671.x] [PMID: 16611233]

[218]
Hirakata Y, Srikumar R, Poole K, et al. Multidrug efflux systems play an important role in the invasiveness of Pseudomonas aeruginosa. J Exp Med  2002; 196(1): 109-18.
 [http://dx.doi.org/10.1084/jem.20020005] [PMID: 12093875]

[219]
Jerse AE, Sharma ND, Simms AN, Crow ET, Snyder LA, Shafer WM. A gonococcal efflux pump system enhances bacterial survival in a female mouse model of genital tract infection. Infect Immun  2003; 71(10): 5576-82.
 [http://dx.doi.org/10.1128/IAI.71.10.5576-5582.2003] [PMID: 14500476]

[220]
Koronakis V, Hughes C. Synthesis, maturation and export of the E. coli hemolysin. Med Microbiol Immunol  1996; 185(2): 65-71.

[221]
Binet R, Létoffé S, Ghigo JM, Delepelaire P, Wandersman C. Protein Secretion by Gram-Negative Bacterial ABC exporters-a review. Gene.  1997.

[222]
Lee VT, Schneewind O. Protein secretion and the pathogenesis of bacterial infections. Genes Dev  2001; 15(14): 1725-52.
 [http://dx.doi.org/10.1101/gad.896801]

[223]
Bhakdi S, Mackman N, Menestrina G, et al. The hemolysin of Escherichia coli. Eur J Epidemiol  1988; 4(2): 135-43.
 [http://dx.doi.org/10.1007/BF00144740] [PMID: 3042445]

[224]
Gilson L, Mahanty HK, Kolter R. Genetic analysis of an MDR-like export system: The secretion of colicin V. EMBO J  1990; 9(12): 3875-84.
 [http://dx.doi.org/10.1002/j.1460-2075.1990.tb07606.x] [PMID: 2249654]

[225]
Boardman BK, Fullner Satchell KJ. Vibrio Cholerae strains with mutations in an atypical type I secretion system accumulate RTX toxin intracellularly. J Bacteriol  2004; 186(23): 8137-43.
 [http://dx.doi.org/10.1128/JB.186.23.8137-8143.2004] [PMID: 15547287]

[226]
Locher KP. Structure and mechanism of ATP-binding cassette transporters. Philos Trans R Soc Lond B Biol Sci  2009; 364(1514): 239-45.
 [http://dx.doi.org/10.1098/rstb.2008.0125] [PMID: 18957379]

[227]
Szakács G, Váradi A, Özvegy-Laczka C, Sarkadi B. The role of ABC transporters in drug absorption, distribution, metabolism, excretion and toxicity (ADME-Tox). Drug Discov Today  2008; 13(9-10): 379-93.
 [http://dx.doi.org/10.1016/j.drudis.2007.12.010] [PMID: 18468555]

[228]
Lubelski J, Konings WN, Driessen AJM. Distribution and physiology of ABC-type transporters contributing to multidrug resistance in bacteria. Microbiol Mol Biol Rev  2007; 71(3): 463-76.
 [http://dx.doi.org/10.1128/MMBR.00001-07] [PMID: 17804667]

[229]
Kuroda T, Tsuchiya T. Multidrug efflux transporters in the MATE family. Biochim Biophys Acta Proteins Proteomics  2009; 1794(5): 763-8.
 [http://dx.doi.org/10.1016/j.bbapap.2008.11.012] [PMID: 19100867]

[230]
Kumar S, Mukherjee MM, Varela MF. Modulation of bacterial multidrug resistance efflux pumps of the major facilitator superfamily. Int J Bacteriol  2013; 2013: 1-15.
 [http://dx.doi.org/10.1155/2013/204141] [PMID: 25750934]

[231]
Yan N. Structural biology of the major facilitator superfamily transporters. Annu Rev Biophys  2015; 44(1): 257-83.
 [http://dx.doi.org/10.1146/annurev-biophys-060414-033901] [PMID: 26098515]

[232]
Law CJ, Maloney PC, Wang DN. Ins and outs of major facilitator superfamily antiporters. Annu Rev Microbiol  2008; 62(1): 289-305.
 [http://dx.doi.org/10.1146/annurev.micro.61.080706.093329] [PMID: 18537473]

[233]
Saier J. SMR-type multidrug resistance pumps. Curr Opin Drug Discov Devel 2001.

[234]
Tseng TT, Gratwick KS, Kollman J, et al. The RND permease superfamily: An ancient, ubiquitous and diverse family that includes hu-man disease and development proteins. J Mol Microbiol Biotechnol  1999; 1(1): 107-25.
 [PMID: 10941792]

[235]
Du D, Wang Z, James NR, et al. Structure of the AcrAB–TolC multidrug efflux pump. Nature  2014; 509(7501): 512-5.
 [http://dx.doi.org/10.1038/nature13205] [PMID: 24747401]

[236]
Yamaguchi A, Nakashima R, Sakurai K. Structural basis of RND-type multidrug exporters. Front Microbiol  2015; 6: 327.
 [http://dx.doi.org/10.3389/fmicb.2015.00327] [PMID: 25941524]

[237]
Daury L, Orange F, Taveau JC, et al. Tripartite assembly of RND multidrug efflux pumps. Nat Commun 2016.

[238]
Hassan KA, Liu Q, Henderson PJF, Paulsen IT. Homologs of the Acinetobacter baumannii AceI transporter represent a new family of bacterial multidrug efflux systems. MBio  2015; 6(1): e01982-14.
 [http://dx.doi.org/10.1128/mBio.01982-14] [PMID: 25670776]

[239]
Chitsaz M, Brown MH. The role played by drug efflux pumps in bacterial multidrug resistance. Essays Biochem  2017; 61(1): 127-39.
 [http://dx.doi.org/10.1042/EBC20160064] [PMID: 28258236]

[240]
Hassan KA, Liu Q, Elbourne LDH, et al. Pacing across the membrane: The novel PACE family of efflux pumps is widespread in Gram-negative pathogens. Res Microbiol  2018; 169(7-8): 450-4.
 [http://dx.doi.org/10.1016/j.resmic.2018.01.001] [PMID: 29409983]

[241]
Handzlik J, Matys A, Kieć-Kononowicz K. Recent advances in multi-drug resistance (MDR) efflux pump inhibitors of grampositive bacteria S. aureus. Antibiotics  2(1): 28-45.

[242]
Kobayashi N, Nishino K, Yamaguchi A. Novel macrolide-specific ABC-type efflux transporter in Escherichia coli. J Bacteriol  2001; 183(19): 5639-44.
 [http://dx.doi.org/10.1128/JB.183.19.5639-5644.2001] [PMID: 11544226]

[243]
Okada U, Yamashita E, Neuberger A, Morimoto M, van Veen HW, Murakami S. Crystal structure of tripartite-type ABC transporter MacB from Acinetobacter baumannii. Nat Commun  2017; 8(1): 1336.
 [http://dx.doi.org/10.1038/s41467-017-01399-2] [PMID: 29109439]

[244]
Brown MH, Paulsen IT, Skurray RA. The multidrug efflux protein NorM is a prototype of a new family of transporters. Mol Microbiol  1999; 31(1): 394-5.
 [http://dx.doi.org/10.1046/j.1365-2958.1999.01162.x] [PMID: 9987140]

[245]
Morita Y, Kodama K, Shiota S, et al. NorM, a putative multidrug efflux protein, of Vibrio parahaemolyticus and its homolog in Esche-richia coli. Antimicrob Agents Chemother  1998; 42(7): 1778-82.
 [http://dx.doi.org/10.1128/AAC.42.7.1778] [PMID: 9661020]

[246]
Bentley J, Hyatt LS, Ainley K, Parish JH, Herbert RB, White GR. Cloning and sequence analysis of an Escherichia coli gene conferring bicyclomycin resistance. Gene  1993; 127(1): 117-20.
 [http://dx.doi.org/10.1016/0378-1119(93)90625-D] [PMID: 8486276]

[247]
Lomovskaya O, Lewis K. Emr, an Escherichia coli locus for multidrug resistance. Proc Natl Acad Sci USA  1992; 89(19): 8938-42.
 [http://dx.doi.org/10.1073/pnas.89.19.8938]

[248]
Naroditskaya V, Schlosser MJ, Fang NY, Lewis K. An E. coli gene emrd is involved in adaptation to low energy shock. Biochem Biophys Res Commun  1993; 196(2): 803-9.

[249]
De Rossi E, Branzoni M, Cantoni R, Milano A, Riccardi G, Ciferri O. mmr, a Mycobacterium tuberculosis gene conferring resistance to small cationic dyes and inhibitors. J Bacteriol  1998; 180(22): 6068-71.
 [http://dx.doi.org/10.1128/JB.180.22.6068-6071.1998] [PMID: 9811672]

[250]
Paulsen IT, Littlejohn TG, Rådström P, et al. The 3′ conserved segment of integrons contains a gene associated with multidrug resistance to antiseptics and disinfectants. Antimicrob Agents Chemother  1993; 37(4): 761-8.
 [http://dx.doi.org/10.1128/AAC.37.4.761] [PMID: 8494372]

[251]
Purewal AS. Nucleotide sequence of the ethidium efflux gene from Escherichia coli. FEMS Microbiol Lett  1991; 82(2): 229-32.
 [http://dx.doi.org/10.1111/j.1574-6968.1991.tb04870.x] [PMID: 1936950]

[252]
Yerushalmi H, Lebendiker M, Schuldiner S. EmrE, an Escherichia coli 12-kDa multidrug transporter, exchanges toxic cations and H+ and is soluble in organic solvents. J Biol Chem  1995; 270(12): 6856-63.
 [http://dx.doi.org/10.1074/jbc.270.12.6856] [PMID: 7896833]

[253]
Poole K. Efflux-mediated multiresistance in gram-negative bacteria. Clin Microbiol Infect  2004; 10(1): 12-26.
 [http://dx.doi.org/10.1111/j.1469-0691.2004.00763.x] [PMID: 14706082]

[254]
Li J, Wehmeyer G, Lovell S, Battaile KP, Egan SM. 1.65 Å resolution structure of the arac-family transcriptional activator toxt from Vibrio Cholerae. Acta Crystallogr F Struct Biol Commun  2016; 72(Pt 9): 726-31.

[255]
Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria: An update. Drugs  2009; 69(12): 1555-623.
 [http://dx.doi.org/10.2165/11317030-000000000-00000] [PMID: 19678712]

[256]
Du D, van Veen HW, Murakami S, Pos KM, Luisi BF. Structure, mechanism and cooperation of bacterial multidrug transporters. Curr Opin Struct Biol  2015; 33: 76-91.
 [http://dx.doi.org/10.1016/j.sbi.2015.07.015] [PMID: 26282926]

[257]
Symmons MF, Marshall RL, Bavro VN. Architecture and roles of periplasmic adaptor proteins in tripartite assemblies. Front Microbiol  2015; 6: 513.
 [http://dx.doi.org/10.3389/fmicb.2015.00513] [PMID: 26074901]

[258]
Neuberger A, Du D, Luisi BF. Structure and mechanism of bacterial tripartite efflux pumps. Res Microbiol  2018; 169(7-8): 401-13.
 [http://dx.doi.org/10.1016/j.resmic.2018.05.003] [PMID: 29787834]

[259]
Hinchliffe P, Symmons MF, Hughes C, Koronakis V. Structure and operation of bacterial tripartite pumps. Annu Rev Microbiol  2013; 67(1): 221-42.
 [http://dx.doi.org/10.1146/annurev-micro-092412-155718] [PMID: 23808339]

[260]
Lorca GL, Barabote RD, Zlotopolski V, et al. Transport capabilities of eleven gram-positive bacteria: Comparative genomic analyses. Biochim Biophys Acta Biomembr  2007; 1768(6): 1342-66.
 [http://dx.doi.org/10.1016/j.bbamem.2007.02.007] [PMID: 17490609]

[261]
Gill MJ, Brenwald NP, Wise R. Identification of an efflux pump gene, pmra, associated with fluoroquinolone resistance in Streptococcus pneumoniae. Antimicrob Agents Chemother  1999; 43(1): 187-9.

[262]
Nikaido H. Structure and Mechanism of RND-Type Multidrug Efflux Pumps. Adv Enzymol Relat Areas Mol Biol 2010.
 [PMID: 21692366]

[263]
Poolman B, Konings WN. Secondary solute transport in bacteria. BBA - Bioenergetics 1993.
 [http://dx.doi.org/10.1016/0005-2728(93)90003-X]

[264]
Krämer R. Functional Principles of Solute Transport Systems: Concepts and Perspectives. BBA - Bioenergetics 1994.

[265]
Henderson PJF. Studies of translocation catalysis. Biosci Rep  1991; 11(6): 477-538.
 [http://dx.doi.org/10.1007/BF01130216] [PMID: 1823597]

[266]
Henderson PJF. The 12-transmembrane helix transporters. Curr Opin Cell Biol  1993; 5(4): 708-21.
 [http://dx.doi.org/10.1016/0955-0674(93)90144-F] [PMID: 8257611]

[267]
Paulsen IT, Brown MH, Skurray RA. Proton-dependent multidrug efflux systems. Microbiol Rev  1996; 60(4): 575-608.
 [http://dx.doi.org/10.1128/mr.60.4.575-608.1996] [PMID: 8987357]

[268]
Kaatz GW, Seo SM. Mechanisms of fluoroquinolone resistance in genetically related strains of Staphylococcus aureus. Antimicrob Agents Chemother  1997; 41(12): 2733-7.
 [http://dx.doi.org/10.1128/AAC.41.12.2733] [PMID: 9420048]

[269]
Piddock LJV. Multidrug-resistance efflux pumps? Not just for resistance. Nat Rev Microbiol  2006; 4(8): 629-36.
 [http://dx.doi.org/10.1038/nrmicro1464] [PMID: 16845433]

[270]
Drlica K, Hiasa H, Kerns R, Malik M, Mustaev A, Zhao X. Quinolones: Action and resistance updated. Curr Top Med Chem  2009; 9(11): 981-98.
 [http://dx.doi.org/10.2174/156802609789630947] [PMID: 19747119]

[271]
Li XZ, Livermore DM, Nikaido H. Role of Efflux Pump(s) in Intrinsic Resistance of Pseudomonas aeruginosa: Resistance to Tetracycline, Chloramphenicol, and Norfloxacin. Antimicrob Agents Chemother 1994.

[272]
Poole K, Krebes K, McNally C, Neshat S. Multiple antibiotic resistance in Pseudomonas aeruginosa: Evidence for involvement of an efflux operon. J Bacteriol  1993; 175(22): 7363-72.
 [http://dx.doi.org/10.1128/jb.175.22.7363-7372.1993] [PMID: 8226684]

[273]
Livermore DM. Linezolid in vitro: Mechanism and antibacterial spectrum. J Antimicrob Chemother  2003; 51(90002) (Suppl. 2): 9ii-16.
 [http://dx.doi.org/10.1093/jac/dkg249] [PMID: 12730138]

[274]
Higgins CF. ABC transporters: From microorganisms to man. Annu Rev Cell Biol  1992; 8(1): 67-113.
 [http://dx.doi.org/10.1146/annurev.cb.08.110192.000435] [PMID: 1282354]

[275]
Fath MJ, Kolter R. ABC transporters: Bacterial exporters. Microbiol Rev  1993; 57(4): 995-1017.
 [http://dx.doi.org/10.1128/mr.57.4.995-1017.1993] [PMID: 8302219]

[276]
Jones PM, O’Mara ML, George AM. ABC transporters: A riddle wrapped in a mystery inside an enigma. Trends Biochem Sci  2009; 34(10): 520-31.
 [http://dx.doi.org/10.1016/j.tibs.2009.06.004] [PMID: 19748784]

[277]
Rees DC, Johnson E, Lewinson O. ABC transporters: The power to change. Nat Rev Mol Cell Biol  2009; 10(3): 218-27.
 [http://dx.doi.org/10.1038/nrm2646] [PMID: 19234479]

[278]
Kast C, Canfield V, Levenson R, Gros P. Transmembrane organization of mouse P-glycoprotein determined by epitope insertion and immunofluorescence. J Biol Chem  1996; 271(16): 9240-8.
 [http://dx.doi.org/10.1074/jbc.271.16.9240] [PMID: 8621583]

[279]
Van Veen HW, Venema K, Bolhuis H, et al. Multidrug resistance mediated by a bacterial homolog of the human multidrug transporter MDR1. Proc Natl Acad Sci USA  1996; 93(20): 10668-72.
 [http://dx.doi.org/10.1073/pnas.93.20.10668]

[280]
Lubelski J, Mazurkiewicz P, van Merkerk R, Konings WN, Driessen AJM. ydaG and ydbA of Lactococcus lactis encode a heterodimeric ATP-binding cassette-type multidrug transporter. J Biol Chem  2004; 279(33): 34449-55.
 [http://dx.doi.org/10.1074/jbc.M404072200] [PMID: 15192086]

[281]
Huda N, Lee EW, Chen J, et al. Molecular cloning and characterization of an ABC multidrug efflux pump, VcaM, in Non-O1 Vibrio Cholerae. Antimicrob Agents Chemother  2003; 47(8): 2413-7.
 [http://dx.doi.org/10.1128/AAC.47.8.2413-2417.2003] [PMID: 12878498]

[282]
Ehrmann M, Ehrle R, Hofmann E, Boos W, Schlösser A. The ABC maltose transporter. Mol Microbiol  1998; 29(3): 685-94.
 [http://dx.doi.org/10.1046/j.1365-2958.1998.00915.x] [PMID: 9723909]

[283]
Alloing G, de Philip P, Claverys JP. Three highly homologous membrane-bound lipoproteins participate in oligopeptide transport by the Ami system of the gram-positive Streptococcus pneumoniae. J Mol Biol  1994; 241(1): 44-58.
 [http://dx.doi.org/10.1006/jmbi.1994.1472] [PMID: 8051706]

[284]
Ross JI, Eady EA, Cove JH, Baumberg S. Minimal functional system required for expression of erythromycin resistance by msrA in Staphylococcus aureus RN4220. Gene  1996; 183(1-2): 143-8.
 [http://dx.doi.org/10.1016/S0378-1119(96)00541-0] [PMID: 8996099]

[285]
Saurin W, Hofnung M, Dassa E. Getting in or out: Early segregation between importers and exporters in the evolution of ATP-Binding Cassette (ABC) transporters. J Mol Evol  1999; 48(1): 22-41.

[286]
Köhler T, Pechère JC, Plésiat P. Bacterial antibiotic efflux systems of medical importance. CMLS. Cell Mol Life Sci  1999; 56: 771-8.

[287]
Davidson AL, Dassa E, Orelle C, Chen J. Structure, function, and evolution of bacterial ATP-binding cassette systems. Microbiol Mol Biol Rev  2008; 72(2): 317-64.
 [http://dx.doi.org/10.1128/MMBR.00031-07] [PMID: 18535149]

[288]
Lage H. ABC-transporters: Implications on drug resistance from microorganisms to human cancers. Int J Antimicrob Agents  2003; 22(3): 188-99.
 [http://dx.doi.org/10.1016/S0924-8579(03)00203-6] [PMID: 13678820]

[289]
Bolhuis H, van Veen HW, Brands JR, et al. Energetics and mechanism of drug transport mediated by the lactococcal multidrug transporter LmrP. J Biol Chem  1996; 271(39): 24123-8.
 [http://dx.doi.org/10.1074/jbc.271.39.24123] [PMID: 8798651]

[290]
Kaur P, Russell J. Biochemical coupling between the DrrA and DrrB proteins of the doxorubicin efflux pump of Streptomyces peucetius. J Biol Chem  1998; 273(28): 17933-9.
 [http://dx.doi.org/10.1074/jbc.273.28.17933] [PMID: 9651400]

[291]
Ross JI, Eady EA, Cove JH, Cunliffe WJ, Baumberg S, Wootton JC. Inducible erythromycin resistance in staphlyococci is encoded by a member of the ATP-binding transport super-gene family. Mol Microbiol  1990; 4(7): 1207-14.
 [http://dx.doi.org/10.1111/j.1365-2958.1990.tb00696.x] [PMID: 2233255]

[292]
Singh K V, Weinstock GM, Murray BE. An Enterococcus faecalis ABC homologue (Lsa) is required for the resistance of this species to clindamycin and quinupristin-dalfopristin. Antimicrob Agents Chemother  2002; 46(6): 1845-50.
 [http://dx.doi.org/10.1128/AAC.46.6.1845-1850.2002]

[293]
Borges-Walmsley MI. McKEEGAN KS, Walmsley AR. Structure and function of efflux pumps that confer resistance to drugs. Biochem J  2003; 376(2): 313-38.
 [http://dx.doi.org/10.1042/bj20020957] [PMID: 13678421]

[294]
Morita Y, Kataoka A, Shiota S, Mizushima T, Tsuchiya T. NorM of vibrio parahaemolyticus is an Na(+)-driven multidrug efflux pump. J Bacteriol  2000; 182(23): 6694-7.
 [http://dx.doi.org/10.1128/JB.182.23.6694-6697.2000] [PMID: 11073914]

[295]
Rouquette-Loughlin C, Dunham SA, Kuhn M, Balthazar JT, Shafer WM. The NorM efflux pump of Neisseria gonorrhoeae and Neisseria meningitidis recognizes antimicrobial cationic compounds. J Bacteriol  2003; 185(3): 1101-6.
 [http://dx.doi.org/10.1128/JB.185.3.1101-1106.2003] [PMID: 12533487]

[296]
Yang S, Clayton SR, Zechiedrich EL. Relative contributions of the AcrAB, MdfA and NorE efflux pumps to quinolone resistance in Escherichia coli. J Antimicrob Chemother  2003; 51(3): 545-56.
 [http://dx.doi.org/10.1093/jac/dkg126] [PMID: 12615854]

[297]
Pao SS, Paulsen IT, Saier MH Jr. Major facilitator superfamily. Microbiol Mol Biol Rev  1998; 62(1): 1-34.
 [http://dx.doi.org/10.1128/MMBR.62.1.1-34.1998] [PMID: 9529885]

[298]
Reddy VS, Shlykov MA, Castillo R, Sun EI, Saier MH. The major facilitator superfamily (MFS) revisited. FEBS J  2012; 279(11): 2022-35.
 [http://dx.doi.org/10.1111/j.1742-4658.2012.08588.x]

[299]
Goswitz VC, Brooker RJ. Structural features of the uniporter/symporter/antiporter superfamily. Protein Sci  1995; 4(3): 534-7.
 [http://dx.doi.org/10.1002/pro.5560040319] [PMID: 7795534]

[300]
Piddock LJV. Clinically relevant chromosomally encoded multidrug resistance efflux pumps in bacteria. Clin Microbiol Rev  2006; 19(2): 382-402.
 [http://dx.doi.org/10.1128/CMR.19.2.382-402.2006] [PMID: 16614254]

[301]
Yoshida H, Bogaki M, Nakamura S, Ubukata K, Konno M. Nucleotide sequence and characterization of the Staphylococcus aureus norA gene, which confers resistance to quinolones. J Bacteriol  1990; 172(12): 6942-9.
 [http://dx.doi.org/10.1128/jb.172.12.6942-6949.1990] [PMID: 2174864]

[302]
Marger MD, Saier MH. A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. Trends Biochem Sci  1993; 18(1): 13-20.
 [http://dx.doi.org/10.1016/0968-0004(93)90081-w]

[303]
Henderson PJF. Sugar transport proteins. Curr Opin Struct Biol  1991; 1(4): 590-601.
 [http://dx.doi.org/10.1016/S0959-440X(05)80082-X]

[304]
Vishwakarma P, Banerjee A, Pasrija R, Prasad R, Lynn AM. Phylogenetic and conservation analyses of MFS transporters. 3 Biotech  2018; 8(11): 462.
 [http://dx.doi.org/10.1007/s13205-018-1476-8]

[305]
Saier MH Jr, Paulsen IT. Phylogeny of multidrug transporters. Semin Cell Dev Biol  2001; 12(3): 205-13.
 [http://dx.doi.org/10.1006/scdb.2000.0246] [PMID: 11428913]

[306]
Paulsen IT, Brown MH, Littlejohn TG, Mitchell BA, Skurray RA. Multidrug resistance proteins QacA and QacB from Staphylococcus aureus: Membrane topology and identification of residues involved in substrate specificity. Proc Natl Acad Sci USA  1996; 938: 3630-5.
 [http://dx.doi.org/10.1073/pnas.93.8.3630]

[307]
Tennent JM, Lyon BR, Midgley M, Jones IG, Purewal AS, Skurray RA. Physical and biochemical characterization of the qacA gene encoding antiseptic and disinfectant resistance in Staphylococcus aureus. J Gen Microbiol  1989; 135(1): 1-10.
 [PMID: 2778425]

[308]
Clancy J, Petitpas J, Dib-Hajj F, et al. Molecular cloning and functional analysis of a novel macrolide‐resistance determinant, mefA, from Streptococcus pyogenes. Mol Microbiol  1996; 22(5): 867-79.
 [http://dx.doi.org/10.1046/j.1365-2958.1996.01521.x] [PMID: 8971709]

[309]
Chopra I, Roberts M. Tetracycline antibiotics: Mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev  2001; 65(2): 232-60.
 [http://dx.doi.org/10.1128/MMBR.65.2.232-260.2001] [PMID: 11381101]

[310]
Kumar A, Schweizer H. Bacterial resistance to antibiotics: Active efflux and reduced uptake. Adv Drug Deliv Rev  2005; 57(10): 1486-513.
 [http://dx.doi.org/10.1016/j.addr.2005.04.004] [PMID: 15939505]

[311]
Korkhov VM, Tate CG. Electron crystallography reveals plasticity within the drug binding site of the small multidrug transporter EmrE. J Mol Biol  2008; 377(4): 1094-103.
 [http://dx.doi.org/10.1016/j.jmb.2008.01.056] [PMID: 18295794]

[312]
Ma C, Chang G. Structure of the multidrug efflux transporter emre from Escherichia coli. Proc Natl Acad Sci USA  2004; 101(9): 2852-7.
 [http://dx.doi.org/10.1073/pnas.0400137101]

[313]
Paulsen IT, Skurray RA, Tam R, et al. The SMR family: A novel family of multidrug efflux proteins involved with the efflux of lipophilic drugs. Mol Microbiol  1996; 19(6): 1167-75.
 [http://dx.doi.org/10.1111/j.1365-2958.1996.tb02462.x] [PMID: 8730859]

[314]
Bay DC, Rommens KL, Turner RJ. Small multidrug resistance proteins: A multidrug transporter family that continues to grow. Biochim Biophys Acta Biomembr  2008; 1778(9): 1814-38.
 [http://dx.doi.org/10.1016/j.bbamem.2007.08.015] [PMID: 17942072]

[315]
Putman M, van Veen HW, Konings WN. Molecular properties of bacterial multidrug transporters. Microbiol Mol Biol Rev  2000; 64(4): 672-93.
 [http://dx.doi.org/10.1128/MMBR.64.4.672-693.2000] [PMID: 11104814]

[316]
Grinius L, Dreguniene G, Goldberg EB, Liao CH, Projan SJ. A staphylococcal multidrug resistance gene product is a member of a new protein family. Plasmid  1992; 27(2): 119-29.
 [http://dx.doi.org/10.1016/0147-619X(92)90012-Y] [PMID: 1615062]

[317]
Schuldiner S, Lebendiker M, Yerushalmi H. EmrE, the smallest ion-coupled transporter, provides a unique paradigm for structure-function studies. J Exp Biol  1997; 200(2): 335-41.
 [http://dx.doi.org/10.1242/jeb.200.2.335] [PMID: 9050242]

[318]
Bay DC, Turner RJ. Diversity and evolution of the small multidrug resistance protein family. BMC Evol Biol  2009; 9(1): 140.
 [http://dx.doi.org/10.1186/1471-2148-9-140] [PMID: 19549332]

[319]
Hansen LH, Johannesen E, Burmølle M, Sørensen AH, Sørensen SJ. Plasmid-encoded multidrug efflux pump conferring resistance to olaquindox in Escherichia coli. Antimicrob Agents Chemother  2004; 48(9): 3332-7.
 [http://dx.doi.org/10.1128/AAC.48.9.3332-3337.2004] [PMID: 15328093]

[320]
Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann Med  2007; 39(3): 162-76.
 [http://dx.doi.org/10.1080/07853890701195262] [PMID: 17457715]

[321]
Zgurskaya HI, Yamada Y, Tikhonova EB, Ge Q, Krishnamoorthy G. Structural and functional diversity of bacterial membrane fusion proteins. Biochim Biophys Acta Proteins Proteomics  2009; 1794(5): 794-807.
 [http://dx.doi.org/10.1016/j.bbapap.2008.10.010] [PMID: 19041958]

[322]
Poole K. Multidrug efflux pumps and antimicrobial resistance in Pseudomonas aeruginosa and related organisms. J Mol Microbiol Biotechnol  2001; 3(2): 255-64.
 [PMID: 11321581]

[323]
Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. Molecular cloning and characterization of acrA and acrE genes of Escherichia coli. J Bacteriol  1993; 175(19): 6299-313.
 [http://dx.doi.org/10.1128/jb.175.19.6299-6313.1993] [PMID: 8407802]

[324]
Ma D, Cook DN, Alberti M, Pon NG, Nikaido H, Hearst JE. Genes acrA and acrB encode a stress-induced efflux system of Escherichia coli. Mol Microbiol  1995; 16(1): 45-55.
 [http://dx.doi.org/10.1111/j.1365-2958.1995.tb02390.x] [PMID: 7651136]

[325]
Murakami S, Nakashima R, Yamashita E, Yamaguchi A. Crystal structure of bacterial multidrug efflux transporter AcrB. Nature  2002; 419(6907): 587-93.
 [http://dx.doi.org/10.1038/nature01050] [PMID: 12374972]

[326]
Sennhauser G, Bukowska MA, Briand C, Grütter MG. Crystal structure of the multidrug exporter MexB from Pseudomonas aeruginosa. J Mol Biol  2009; 389(1): 134-45.
 [http://dx.doi.org/10.1016/j.jmb.2009.04.001] [PMID: 19361527]

[327]
Guan L, Ehrmann M, Yoneyama H, Nakae T. Membrane topology of the xenobiotic-exporting subunit, MexB, of the MexA,B-OprM extrusion pump in Pseudomonas aeruginosa. J Biol Chem  1999; 274(15): 10517-22.
 [http://dx.doi.org/10.1074/jbc.274.15.10517] [PMID: 10187844]

[328]
Li XZ, Nikaido H, Poole K. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob Agents Chemother  1995; 39(9): 1948-53.
 [http://dx.doi.org/10.1128/AAC.39.9.1948] [PMID: 8540696]

[329]
Godoy P, Molina-Henares AJ, De La Torre J, Duque E, Ramos JL. Characterization of the RND family of multidrug efflux pumps: In silico to in vivo confirmation of four functionally distinct subgroups. Microb Biotechnol 2010. Microb Biotechnol  2010; 3(6): 691-700.
 [http://dx.doi.org/10.1111/j.1751-7915.2010.00189.x]

[330]
Kinana AD, Vargiu A V, May T, Nikaido H. Aminoacyl β-Naphthylamides as substrates and modulators of AcrB multidrug efflux pump. Proc Natl Acad Sci USA  2016; 113(5): 1405-0.
 [http://dx.doi.org/10.1073/pnas.1525143113]

[331]
Noguchi N, Okada H, Narui K, Sasatsu M. Comparison of the nucleotide sequence and expression of norA genes and microbial susceptibility in 21 strains of Staphylococcus aureus. Microb Drug Resist  2004; 10(3): 197-203.
 [http://dx.doi.org/10.1089/mdr.2004.10.197] [PMID: 15383162]

[332]
Schmitz FJ, Hertel B, Hofmann B, et al. Relationship between mutations in the coding and promoter regions of the norA genes in 42 unrelated clinical isolates of Staphylococcus aureus and the MICs of norfloxacin for these strains. J Antimicrob Chemother  1998; 42(4): 561-3.
 [http://dx.doi.org/10.1093/jac/42.4.561] [PMID: 9818767]

[333]
Sierra JM, Ruiz J, Vila J, Vila J. Prevalence of two different genes encoding NorA in 23 clinical strains of Staphylococcus aureus. J Antimicrob Chemother  2000; 46(1): 145-6.
 [http://dx.doi.org/10.1093/jac/46.1.145] [PMID: 10882706]

[334]
Neyfakh AA, Borsch CM, Kaatz GW. Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux trans-porter. Antimicrob Agents Chemother  1993; 37(1): 128-9.
 [http://dx.doi.org/10.1128/AAC.37.1.128] [PMID: 8431010]

[335]
Kaatz GW, Seo SM, Ruble CA. Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus. Antimicrob Agents Chemother  1993; 37(5): 1086-94.
 [http://dx.doi.org/10.1128/AAC.37.5.1086] [PMID: 8517696]

[336]
Ng EY, Trucksis M, Hooper DC. Quinolone resistance mediated by norA: Physiologic characterization and relationship to flqB, a quino-lone resistance locus on the Staphylococcus aureus chromosome. Antimicrob Agents Chemother  1994; 38(6): 1345-55.
 [http://dx.doi.org/10.1128/AAC.38.6.1345] [PMID: 8092836]

[337]
Poole K. Efflux-mediated resistance to fluoroquinolones in gram-negative bacteria. Antimicrob Agents Chemother  2000; 44(9): 2233-41.
 [http://dx.doi.org/10.1128/AAC.44.9.2233-2241.2000] [PMID: 10952561]

[338]
Palazzotti D, Bissaro M, Bolcato G, et al. Deciphering the molecular recognition mechanism of multidrug resistance Staphylococcus aureus NorA efflux pump using a supervised molecular dynamics approach. Int J Mol Sci  2019; 20(16): 4041.
 [http://dx.doi.org/10.3390/ijms20164041] [PMID: 31430864]

[339]
Schindler BD, Jacinto P, Kaatz GW. Inhibition of drug efflux pumps in Staphylococcus aureus: Current status of potentiating existing antibiotics. Future Microbiol  2013; 8(4): 491-507.
 [http://dx.doi.org/10.2217/fmb.13.16]

[340]
Miyamae S, Nikaido H, Tanaka Y, Yoshimura F. Active efflux of norfloxacin by Bacteroides fragilis. Antimicrob Agents Chemother  1998; 42(8): 2119-21.
 [http://dx.doi.org/10.1128/AAC.42.8.2119] [PMID: 9687419]

[341]
Kaatz GW, Seo SM, Ruble CA. Mechanisms of fluoroquinolone resistance in Staphylococcus aureus. J Infect Dis  1991; 163(5): 1080-6.
 [http://dx.doi.org/10.1093/infdis/163.5.1080] [PMID: 1850442]

[342]
Couto I, Costa SS, Viveiros M, Martins M, Amaral L. Efflux-mediated response of Staphylococcus aureus exposed to ethidium bromide. J Antimicrob Chemother  2008; 62(3): 504-13.
 [http://dx.doi.org/10.1093/jac/dkn217] [PMID: 18511413]

[343]
Kaatz GW, Seo SM. Effect of substrate exposure and other growth condition manipulations on norA expression. J Antimicrob Chemother  2004; 54(2): 364-9.
 [http://dx.doi.org/10.1093/jac/dkh341] [PMID: 15231765]

[344]
Fournier B, Truong-Bolduc QC, Zhang X, Hooper DC. A mutation in the 5′ untranslated region increases stability of norA mRNA, encoding a multidrug resistance transporter of Staphylococcus aureus. J Bacteriol  2001; 183(7): 2367-71.
 [http://dx.doi.org/10.1128/JB.183.7.2367-2371.2001] [PMID: 11244079]

[345]
DeMarco CE, Cushing LA, Frempong-Manso E, Seo SM, Jaravaza TAA, Kaatz GW. Efflux-related resistance to norfloxacin, dyes, and biocides in bloodstream isolates of Staphylococcus aureus. Antimicrob Agents Chemother  2007; 51(9): 3235-9.
 [http://dx.doi.org/10.1128/AAC.00430-07] [PMID: 17576828]

[346]
Huet AA, Raygada JL, Mendiratta K, Seo SM, Kaatz GW. Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes. Microbiology  2008; 154(10): 3144-53.
 [http://dx.doi.org/10.1099/mic.0.2008/021188-0] [PMID: 18832320]

[347]
Cozzarelli NR. DNA gyrase and the supercoiling of DNA. Science  1980; 207(4434): 953-60.
 [http://dx.doi.org/10.1126/science.6243420]

[348]
Hooper DC. Mechanisms of fluoroquinolone resistance. Drug Resist Updat  1999; 2(1): 38-55.
 [http://dx.doi.org/10.1054/drup.1998.0068] [PMID: 11504468]

[349]
Smith HJ, Nichol KA, Hoban DJ, Zhanel GG. Dual activity of fluoroquinolones against Streptococcus Pneumoniae: The facts behind the claims. J Antimicrob Chemother  2002; 49(6): 893-5.
 [http://dx.doi.org/10.1093/jac/dkf047] [PMID: 12039880]

[350]
Gutierrez A, Stokes J, Matic I. Our evolving understanding of the mechanism of quinolones. Antibiotics  2018; 7(2): 32.
 [http://dx.doi.org/10.3390/antibiotics7020032] [PMID: 29642475]

[351]
Wang JC. DNA topoisomerases. Annu Rev Biochem  1996; 65(1): 635-92.
 [http://dx.doi.org/10.1146/annurev.bi.65.070196.003223] [PMID: 8811192]

[352]
Ezelarab HAA, Abbas SH, Hassan HA, Abuo-Rahma GEDA. Recent updates of fluoroquinolones as antibacterial agents. Arch Pharm  2018; 351(9): 1800141.
 [http://dx.doi.org/10.1002/ardp.201800141] [PMID: 30048015]

[353]
Zechiedrich EL, Cozzarelli NR. Roles of topoisomerase IV and during replication in Eschericia coli. Genes Dev 1995.
 [http://dx.doi.org/10.1101/gad.9.22.2859]

[354]
Marians KJ, Hiasa H. Mechanism of quinolone action. A drug-induced structural perturbation of the DNA precedes strand cleavage by topoisomerase IV. J Biol Chem  1997; 272(14): 9401-9.
 [http://dx.doi.org/10.1074/jbc.272.14.9401] [PMID: 9083078]

[355]
Blandeau JM. Expanded activity and utility of the new fluoroquinolones: A review. Clin Ther  1999; 21(1): 3-40.
 [http://dx.doi.org/10.1016/S0149-2918(00)88266-1] [PMID: 10090423]

[356]
Schmitz F, Hofmann B, Hansen B, et al. Relationship between ciprofloxacin, ofloxacin, levofloxacin, sparfloxacin and moxifloxacin (BAY 12-8039) MICs and mutations in grlA, grlB, gyrA and gyrB in 116 unrelated clinical isolates of Staphylococcus aureus. J Antimicrob Chemother  1998; 41(4): 481-4.
 [http://dx.doi.org/10.1093/jac/41.4.481] [PMID: 9598779]

[357]
Fisher LM, Heaton VJ. Dual activity of fluoroquinolones against Streptococcus Pneumoniae. J Antimicrob Chemother  2003; 51(2): 463-4.

[358]
Chopra I, Hawkey PM, Hinton M. Tetracyclines, molecular and clinical aspects. J Antimicrob Chemother  1992; 29(3): 245-77.
 [http://dx.doi.org/10.1093/jac/29.3.245] [PMID: 1592696]

[359]
Speer BS, Shoemaker NB, Salyers AA. Bacterial resistance to tetracycline: Mechanisms, transfer, and clinical significance. Clin Microbiol Rev  1992; 5(4): 387-99.
 [http://dx.doi.org/10.1128/CMR.5.4.387] [PMID: 1423217]

[360]
Roberts MC. Tetracycline resistance determinants: Mechanisms of action, regulation of expression, genetic mobility, and distribution. FEMS Microbiol Rev  1996; 19(1): 1-24.
 [http://dx.doi.org/10.1111/j.1574-6976.1996.tb00251.x] [PMID: 8916553]

[361]
Sum PE, Petersen P. Synthesis and structure-activity relationship of novel glycylcycline derivatives leading to the discovery of GAR-936. Bioorganic Med Chem Lett  1999; 9(10): 1459-62.

[362]
Testa RT, Petersen PJ, Jacobus NV, Sum PE, Lee VJ, Tally FP. In vitro and in vivo antibacterial activities of the glycylcyclines, a new class of semisynthetic tetracyclines. Antimicrob Agents Chemother  1993; 37(11): 2270-7.
 [http://dx.doi.org/10.1128/AAC.37.11.2270] [PMID: 8285606]

[363]
Gillespie MT, Lyon BR, Loo LSL, Matthews PR, Stewart PR, Skurray RA. Homologous direct repeat sequences associated with mercury, methicillin, tetracycline and trimethoprim resistance determinants in Staphylococcus aureus. FEMS Microbiol Lett  1987; 43(2): 165-71.
 [http://dx.doi.org/10.1111/j.1574-6968.1987.tb02117.x]

[364]
Needham C, Rahman M, Dyke KGH, Noble WC. An investigation of plasmids from Staphylococcus aureus that mediate resistance to mupirocin and tetracycline. Microbiology  1994; 140(10): 2577-83.
 [http://dx.doi.org/10.1099/00221287-140-10-2577] [PMID: 8000528]

[365]
Schwarz S, Roberts MC, Werckenthin C, Pang Y, Lange C. Tetracycline resistance in Staphylococcus spp. from domestic animals. Vet Microbiol  1998; 63(2-4): 217-27.
 [http://dx.doi.org/10.1016/S0378-1135(98)00234-X] [PMID: 9851000]

[366]
Projan SJ, Novick R. Comparative analysis of five related staphylococcal plasmids. Plasmid  1988; 19(3): 203-21.
 [http://dx.doi.org/10.1016/0147-619X(88)90039-X] [PMID: 2852816]

[367]
Khan SA, Novick RP. Complete nucleotide sequence of pT181, a tetracycline-resistance plasmid from Staphylococcus aureus. Plasmid  1983; 10(3): 251-9.
 [http://dx.doi.org/10.1016/0147-619X(83)90039-2] [PMID: 6657777]

[368]
McMurry LM, Levy S. Tetracycline Resistance in Gram-Positive Bacteria. In: Fischetti VA, Novick RP, Ferretti JJ, Portnoy DA, Rood JI, Eds. Gram-Positive Pathogens;. American Society for Microbiology. Washington, D.C. 2000.

[369]
Brodersen DE, Clemons WM Jr, Carter AP, Morgan-Warren RJ, Wimberly BT, Ramakrishnan V. The structural basis for the action of the antibiotics tetracycline, pactamycin, and hygromycin B on the 30S ribosomal subunit. Cell  2000; 103(7): 1143-54.
 [http://dx.doi.org/10.1016/S0092-8674(00)00216-6] [PMID: 11163189]

[370]
Ginn SL, Brown MH, Skurray RA. Membrane topology of the metal-tetracycline/H+ antiporter TetA(K) from Staphylococcus aureus. J Bacteriol  1997; 179(11): 3786-9.
 [http://dx.doi.org/10.1128/jb.179.11.3786-3789.1997] [PMID: 9171431]

[371]
Yamaguchi A, Udagawa T, Sawai T. Transport of divalent cations with tetracycline as mediated by the transposon Tn10-encoded tetracycline resistance protein. J Biol Chem  1990; 265(9): 4809-13.
 [http://dx.doi.org/10.1016/S0021-9258(19)34044-X] [PMID: 2156856]

[372]
Tamura N, Konishi S, Iwaki S, Kimura-Someya T, Nada S, Yamaguchi A. Complete cysteine-scanning mutagenesis and site-directed chemical modification of the Tn10-encoded metaltetracycline/H+ antiporter. J Biol Chem  2001; 276(23): 20330-9.
 [http://dx.doi.org/10.1074/jbc.M007993200] [PMID: 11278375]

[373]
McAleese F, Petersen P, Ruzin A, et al. A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline. Antimicrob Agents Chemother  2005; 49(5): 1865-71.
 [http://dx.doi.org/10.1128/AAC.49.5.1865-1871.2005] [PMID: 15855508]

[374]
He GX, Kuroda T, Mima T, Morita Y, Mizushima T, Tsuchiya T. An H(+)-coupled multidrug efflux pump, PmpM, a member of the MATE family of transporters, from Pseudomonas aeruginosa. J Bacteriol  2004; 186(1): 262-5.
 [http://dx.doi.org/10.1128/JB.186.1.262-265.2004] [PMID: 14679249]

[375]
Kaatz GW, DeMarco CE, Seo SM. MepR, a repressor of the Staphylococcus aureus MATE family multidrug efflux pump MepA, is a substrate-responsive regulatory protein. Antimicrob Agents Chemother  2006; 50(4): 1276-81.
 [http://dx.doi.org/10.1128/AAC.50.4.1276-1281.2006] [PMID: 16569840]

[376]
Hyde SC, Emsley P, Hartshorn MJ, et al. Structural model of ATP-binding proteing associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature  1990; 346(6282): 362-5.
 [http://dx.doi.org/10.1038/346362a0] [PMID: 1973824]

[377]
Reynolds E, Ross JI, Cove JH. Msr(A) and related macrolide/streptogramin resistance determinants: incomplete transporters? Int J Antimicrob Agents  2003; 22(3): 228-36.
 [http://dx.doi.org/10.1016/S0924-8579(03)00218-8] [PMID: 13678826]

[378]
Novotna G, Adamkova V, Janata J, Melter O, Spizek J. Prevalence of resistance mechanisms against macrolides and lincosamides in methicillin-resistant coagulase-negative staphylococci in the Czech Republic and occurrence of an undefined mechanism of resistance to lincosamides. Antimicrob Agents Chemother  2005; 49(8): 3586-9.
 [http://dx.doi.org/10.1128/AAC.49.8.3586-3589.2005] [PMID: 16048992]

[379]
Ross JI, Farrell AM, Eady EA, Cove JH, Cunliffe WJ. Characterisation and molecular cloning of the novel macrolide-streptogramin B resistance determinant from Staphylococcus epidermidis. J Antimicrob Chemother  1989; 24(6): 851-62.
 [http://dx.doi.org/10.1093/jac/24.6.851] [PMID: 2559912]

[380]
Kerr ID. Sequence analysis of twin ATP binding cassette proteins involved in translational control, antibiotic resistance, and ribonuclease L inhibition. Biochem Biophys Res Commun  2004; 315(1): 166-73.
 [http://dx.doi.org/10.1016/j.bbrc.2004.01.044] [PMID: 15013441]

[381]
Capobianco JO, Goldman RC. Erythromycin and azithromycin transport into Haemophilus influenzae ATCC 19418 under conditions of depressed proton motive force (delta μ H). Antimicrob Agents Chemother  1990; 34(9): 1787-91.
 [http://dx.doi.org/10.1128/AAC.34.9.1787] [PMID: 2178338]

[382]
Kerr ID, Reynolds ED, Cove JH. ABC proteins and antibiotic drug resistance: Is it all about transport? Biochem Soc Trans  2005; 33(Pt 5): 1000-2.
 [http://dx.doi.org/10.1042/BST20051000]

[383]
Wang J. Analysis of macrolide antibiotics, using liquid chromatography-mass spectrometry, in food, biological and environmental matri-ces. Mass Spectrom Rev  2009; 28(1): 50-92.
 [http://dx.doi.org/10.1002/mas.20189]

[384]
Kanoh S, Rubin BK. Mechanisms of action and clinical application of macrolides as immunomodulatory medications. Clin Microbiol Rev  2010; 23(3): 590-615.
 [http://dx.doi.org/10.1128/CMR.00078-09] [PMID: 20610825]

[385]
Tenson T, Lovmar M, Ehrenberg M. The mechanism of action of macrolides, lincosamides and streptogramin B reveals the nascent peptide exit path in the ribosome. J Mol Biol  2003; 330(5): 1005-14.
 [http://dx.doi.org/10.1016/S0022-2836(03)00662-4] [PMID: 12860123]

[386]
Schlünzen F, Zarivach R, Harms J, et al. Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Nature  2001; 413(6858): 814-21.
 [http://dx.doi.org/10.1038/35101544] [PMID: 11677599]

[387]
Guo MT, Yuan QB, Yang J. Insights into the amplification of bacterial resistance to erythromycin in activated sludge. Chemosphere  2015; 136: 79-85.
 [http://dx.doi.org/10.1016/j.chemosphere.2015.03.085]

[388]
Varaldo PE, Montanari MP, Giovanetti E. Genetic elements responsible for erythromycin resistance in streptococci. Antimicrob Agents Chemother  2009; 53(2): 343-53.
 [http://dx.doi.org/10.1128/AAC.00781-08] [PMID: 19001115]

[389]
Liang JH, Han X. Structure-activity relationships and mechanism of action of macrolides derived from erythromycin as antibacterial agents. Curr Top Med Chem  2013; 13(24): 3131-64.
 [http://dx.doi.org/10.2174/15680266113136660223] [PMID: 24200358]

[390]
Ashima KB, Mohanty P. Bacterial efflux pumps involved in multidrug resistance and their inhibitors: Rejuvinating the antimicrobial chemotherapy. Recent Pat Antiinfect Drug Discov  2012; 7(1): 73-89.

[391]
Li XZ, Nikaido H. Efflux-mediated drug resistance in bacteria. Drugs  2004; 64(2): 159-204.
 [http://dx.doi.org/10.2165/00003495-200464020-00004] [PMID: 14717618]

[392]
Zechini B, Versace I. Inhibitors of multidrug resistant efflux systems in bacteria. Recent Pat Antiinfect Drug Discov  2009; 4(1): 37-50.
 [http://dx.doi.org/10.2174/157489109787236256]

[393]
Drlica K. The mutant selection window and antimicrobial resistance. J Antimicrob Chemother  2003; 52(1): 11-7.
 [http://dx.doi.org/10.1093/jac/dkg269] [PMID: 12805267]

[394]
Purssell A, Poole K. Functional characterization of the NfxB repressor of the mexCD-oprJ multidrug efflux operon of Pseudomonas aeruginosa. Microbiology (Reading)  2013; 159(Pt 10): 2058-73.
 [http://dx.doi.org/10.1099/mic.0.069286-0]

[395]
Zeng B, Wang H, Zou L, Zhang A, Yang X, Guan Z. Evaluation and target validation of indole derivatives as inhibitors of the AcrAB-TolC efflux pump. Biosci Biotechnol Biochem  2010; 74(11): 2237-41.
 [http://dx.doi.org/10.1271/bbb.100433] [PMID: 21071837]

[396]
Martins M, Dastidar SG, Fanning S, et al. Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant gram-negative infections: Mechanisms for their direct and indirect activities. Int J Antimicrob Agents  2008; 31(3): 198-208.
 [http://dx.doi.org/10.1016/j.ijantimicag.2007.10.025] [PMID: 18180147]

[397]
Viveiros M, Jesus A, Brito M, et al. Inducement and reversal of tetracycline resistance in Escherichia coli K-12 and expression of pro-ton gradient-dependent multidrug efflux pump genes. Antimicrob Agents Chemother  2005; 49(8): 3578-82.
 [http://dx.doi.org/10.1128/AAC.49.8.3578-3582.2005] [PMID: 16048990]

[398]
Pagès JM, Masi M, Barbe J. Inhibitors of efflux pumps in gram-negative bacteria. Trends Mol Med  2005; 11(8): 382-9.
 [http://dx.doi.org/10.1016/j.molmed.2005.06.006] [PMID: 15996519]

[399]
Van Bambeke F, Pagès J-M, Lee VJ. Inhibitors of bacterial efflux pumps as adjuvants in antibiotic treatments and diagnostic tools for detection of resistance by efflux. Recent Pat Antiinfect Drug Discov  2006; 1(2): 157-75.
 [http://dx.doi.org/10.2174/157489106777452692]

[400]
Tikhonova EB, Yamada Y, Zgurskaya HI. Sequential mechanism of assembly of multidrug efflux pump AcrAB-TolC. Chem Biol  2011; 18(4): 454-63.
 [http://dx.doi.org/10.1016/j.chembiol.2011.02.011] [PMID: 21513882]

[401]
Chollet R, Chevalier J, Bryskier A, Pagès JM. The AcrAB-TolC pump is involved in macrolide resistance but not in telithromycin efflux in Enterobacter aerogenes and Escherichia coli. Antimicrob Agents Chemother  2004; 48(9): 3621-4.
 [http://dx.doi.org/10.1128/AAC.48.9.3621-3624.2004] [PMID: 15328143]

[402]
Rice A, Liu Y, Michaelis ML, Himes RH, Georg GI, Audus KL. Chemical modification of paclitaxel (Taxol) reduces p-glycoprotein interactions and increases permeation across the blood−brain barrier in vitro and in situ. J Med Chem  2005; 48(3): 832-8.
 [http://dx.doi.org/10.1021/jm040114b]

[403]
Hobbs EC, Yin X, Paul BJ, Astarita JL, Storz G. Conserved small protein associates with the multidrug efflux pump AcrB and differentially affects antibiotic resistance. Proc Natl Acad Sci USA  2012; 109(41): 16696-701.
 [http://dx.doi.org/10.1073/pnas.1210093109]

[404]
Chopra I. New developments in tetracycline antibiotics: Glycylcyclines and tetracycline efflux pump inhibitors. Drug Resist Updat  2002; 5(3-4): 119-25.
 [http://dx.doi.org/10.1016/S1368-7646(02)00051-1] [PMID: 12237079]

[405]
Zloh M, Kaatz GW, Gibbons S. Inhibitors of multidrug resistance (MDR) have affinity for MDR substrates. Bioorganic Med Chem Lett  2004; 14(4): 881-5.
 [http://dx.doi.org/10.1016/j.bmcl.2003.12.015]

[406]
Nakashima R, Sakurai K, Yamasaki S, et al. Structural basis for the inhibition of bacterial multidrug exporters. Nature  2013; 500(7460): 102-6.
 [http://dx.doi.org/10.1038/nature12300] [PMID: 23812586]

[407]
Opperman TJ, Kwasny SM, Kim HS, et al. Characterization of a novel pyranopyridine inhibitor of the AcrAB efflux pump of Escherichia coli. Antimicrob Agents Chemother  2014; 58(2): 722-33.
 [http://dx.doi.org/10.1128/AAC.01866-13] [PMID: 24247144]

[408]
Nguyen ST, Kwasny SM, Ding X, et al. Structure-activity relationships of a novel pyranopyridine series of gram-negative bacterial efflux pump inhibitors. Bioorganic Med Chem  2015; 23(9): 2024-34.
 [http://dx.doi.org/10.1016/j.bmc.2015.03.016]

[409]
Opperman TJ, Nguyen ST. Recent advances toward a molecular mechanism of efflux pump inhibition. Front Microbiol  2015; 6: 421.
 [http://dx.doi.org/10.3389/fmicb.2015.00421] [PMID: 25999939]

[410]
Pagès JM, Amaral L, Fanning S. An original deal for new molecule: Reversal of efflux pump activity, a rational strategy to combat gram-negative resistant bacteria. Curr Med Chem  2011; 18(19): 2969-80.
 [http://dx.doi.org/10.2174/092986711796150469] [PMID: 21651484]

[411]
Marquez B. Bacterial efflux systems and efflux pumps inhibitors. Biochimie  2005; 87(12): 1137-47.
 [http://dx.doi.org/10.1016/j.biochi.2005.04.012] [PMID: 15951096]

[412]
Spindler EC, Hale JDF, Giddings TH Jr, Hancock REW, Gill RT. Deciphering the mode of action of the synthetic antimicrobial peptide Bac8c. Antimicrob Agents Chemother  2011; 55(4): 1706-16.
 [http://dx.doi.org/10.1128/AAC.01053-10] [PMID: 21282431]

[413]
Yu Z, Cai Y, Qin W, Lin J, Qiu J. Polymyxin E induces rapid Paenibacillus polymyxa death by damaging cell membrane while Ca2+ can protect cells from damage. PLoS One  2015; 10(8): e0135198.
 [http://dx.doi.org/10.1371/journal.pone.0135198] [PMID: 26252512]

[414]
Ni W, Li Y, Guan J, et al. Effects of efflux pump inhibitors on colistin resistance in multidrug-resistant gram-negative bacteria. Antimicrob Agents Chemother  2016; 60(5): 3215-8.
 [http://dx.doi.org/10.1128/AAC.00248-16] [PMID: 26953203]

[415]
Park YK, Ko KS. Effect of carbonyl cyanide 3-chlorophenylhydrazone (CCCP) on killing Acinetobacter baumannii by colistin. J Microbiol  2015; 53(1): 53-9.
 [http://dx.doi.org/10.1007/s12275-015-4498-5] [PMID: 25557480]

[416]
Mohamed YF, Abou-Shleib HM, Khalil AM, El-Guink NM, El-Nakeeb MA. Membrane permeabilization of colistin toward pandrug resistant gram-negative isolates. Braz J Microbiol  2016; 47(2): 381-8.
 [http://dx.doi.org/10.1016/j.bjm.2016.01.007] [PMID: 26991296]

[417]
Anoushiravani M, Falsafi T, Niknam V. Proton motive force-dependent efflux of tetracycline in clinical isolates of Helicobacter pylori. J Med Microbiol  2009; 58(10): 1309-13.
 [http://dx.doi.org/10.1099/jmm.0.010876-0] [PMID: 19574414]

[418]
Fenosa A, Fusté E, Ruiz L, et al. Role of TolC in Klebsiella oxytoca resistance to antibiotics. J Antimicrob Chemother  2009; 63(4): 668-74.
 [http://dx.doi.org/10.1093/jac/dkp027] [PMID: 19240073]

[419]
Osei Sekyere J, Amoako DG. Carbonyl cyanide mchlorophenylhydrazine (CCCP) reverses resistance to colistin, but not to carbapenems and tigecycline in multidrug-resistant Enterobacteriaceae. Front Microbiol  2017; 8: 228.
 [http://dx.doi.org/10.3389/fmicb.2017.00228] [PMID: 28261184]

[420]
Li XZ, Plésiat P, Nikaido H. The challenge of efflux-mediated antibiotic resistance in gram-negative bacteria. Clin Microbiol Rev  2015; 28(2): 337-418.
 [http://dx.doi.org/10.1128/CMR.00117-14] [PMID: 25788514]

[421]
Huang L, Sun L, Xu G, Xia T. Differential susceptibility to carbapenems Due to the AdeABC efflux pump among nosocomial outbreak isolates of Acinetobacter baumannii in a Chinese Hospital. Diagn Microbiol Infect Dis  2008; 62(3): 326.
 [http://dx.doi.org/10.1016/j.diagmicrobio.2008.06.008]

[422]
Lomovskaya O, Warren MS, Lee A, et al. Identification and characterization of inhibitors of multidrug resistance efflux pumps in Pseu-domonas aeruginosa: Novel agents for combination therapy. Antimicrob Agents Chemother  2001; 45(1): 105-16.
 [http://dx.doi.org/10.1128/AAC.45.1.105-116.2001] [PMID: 11120952]

[423]
Mahamoud A, Chevalier J, Davin-Regli A, Barbe J, Pagès JM. Quinoline derivatives as promising inhibitors of antibiotic efflux pump in multidrug resistant Enterobacter aerogenes isolates. Curr Drug Targets  2006; 7(7): 843-7.
 [http://dx.doi.org/10.2174/138945006777709557] [PMID: 16842215]

[424]
Sánchez P, Le U, Martínez JL. The efflux pump inhibitor Phe-Arg-β-naphthylamide does not abolish the activity of the Stenotrophomonas maltophilia SmeDEF multidrug efflux pump. J Antimicrob Chemother  2003; 51(4): 1042-5.
 [http://dx.doi.org/10.1093/jac/dkg181] [PMID: 12654744]

[425]
Mahmood Y. Current advances in developing inhibitors of bacterial multidrug efflux pumps. Curr Med Chem 2016  2016; 23(10): 1062-81.
 [http://dx.doi.org/10.2174/0929867323666160304150522]

[426]
Dreier J, Ruggerone P. Interaction of antibacterial compounds with RND efflux pumps in Pseudomonas aeruginosa. Front Microbiol  2015; 6: 660.
 [http://dx.doi.org/10.3389/fmicb.2015.00660] [PMID: 26217310]

[427]
Renau TE, Léger R, Flamme EM, et al. Inhibitors of efflux pumps in Pseudomonas aeruginosa potentiate the activity of the fluoroquinolone antibacterial levofloxacin. J Med Chem  1999; 42(24): 4928-31.
 [http://dx.doi.org/10.1021/jm9904598] [PMID: 10585202]

[428]
Askoura M, Mattawa W, Abujamel T, Taher I. Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa. Libyan J Med  2011; 6(1): 5870.
 [http://dx.doi.org/10.3402/ljm.v6i0.5870] [PMID: 21594004]

[429]
Lomovskaya O, Watkins W. Inhibition of efflux pumps as a novel approach to combat drug resistance in bacteria. J Mol Microbiol Biotechnol  2001; 3(2): 225-36.
 [PMID: 11321578]

[430]
Matsumoto Y, Hayama K, Sakakihara S, et al. Evaluation of multidrug efflux pump inhibitors by a new method using microfluidic channels. PLoS One  2011; 6(4): e18547.
 [http://dx.doi.org/10.1371/journal.pone.0018547] [PMID: 21533264]

[431]
Lamers RP, Cavallari JF, Burrows LL. The efflux inhibitor phenylalanine-arginine beta-naphthylamide (PAβN) permeabilizes the outer membrane of gram-negative bacteria. PLoS One  2013; 8(3): e60666.
 [http://dx.doi.org/10.1371/journal.pone.0060666] [PMID: 23544160]

[432]
Tintino SR, Morais-Tintino CD, Campina FF, Costa M. Tannic acid affects the phenotype of Staphylococcus aureus resistant to tetracycline and erythromycin by inhibition of efflux pumps. Bioorg Chem  2017; 74: 197-200.

[433]
Tintino SR, Oliveira-Tintino CDM, Campina FF, et al. Evaluation of the tannic acid inhibitory effect against the NorA efflux pump of Staphylococcus aureus. Microb Pathog  2016; 97: 9-13.
 [http://dx.doi.org/10.1016/j.micpath.2016.04.003]

[434]
Figueredo FG, Ramos ITL, Paz JA, et al. Effect of hydroxyamines derived from lapachol and norlachol against Staphylococcus aureus strains carrying the NorA efflux pump. Infect Genet Evol  2020; 84: 104370.
 [http://dx.doi.org/10.1016/j.meegid.2020.104370] [PMID: 32445918]

[435]
Vargiu A V, Nikaido H. Multidrug binding properties of the AcrB efflux pump characterized by molecular dynamics simulations. Proc Natl Acad Sci USA 2012  2012; 109(50): 20637-42.
 [http://dx.doi.org/10.1073/pnas.1218348109]

[436]
Vargiu AV, Ruggerone P, Opperman TJ, Nguyen ST, Nikaido H. Molecular mechanism of MBX2319 inhibition of Escherichia coli AcrB multidrug efflux pump and comparison with other inhibitors. Antimicrob Agents Chemother  2014; 58(10): 6224-34.
 [http://dx.doi.org/10.1128/AAC.03283-14] [PMID: 25114133]

[437]
Müller RT, Travers T, Cha H, Phillips JL, Gnanakaran S, Pos KM. Switch loop flexibility affects substrate transport of the acrb efflux pump. J Mol Biol  2017; 429(24): 3863-74.
 [http://dx.doi.org/10.1016/j.jmb.2017.09.018]

[438]
Renau TE, Léger R, Filonova L, et al. Conformationally-restricted analogues of efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa. Bioorganic Med Chem Lett  2003; 13(16): 2755-8.
 [http://dx.doi.org/10.1016/S0960-894X(03)00556-0]

[439]
Pagès JM, Amaral L. Mechanisms of drug efflux and strategies to combat them: Challenging the efflux pump of gram-negative bacteria. Biochim Biophys Acta Proteins Proteomics  2009; 1794(5): 826-33.
 [http://dx.doi.org/10.1016/j.bbapap.2008.12.011]

[440]
Sjuts H, Vargiu A V, Kwasny SM, et al. Molecular basis for inhibition of AcrB multidrug efflux pump by novel and powerful pyranopyridine derivatives. Proc Natl Acad Sci USA  2016; 113(13): 3509-14.
 [http://dx.doi.org/10.1073/pnas.1602472113]

[441]
Rathi E, Kumar A, Kini SG. Computational approaches in efflux pump inhibitors: Current status and prospects. Drug Discov Today  2020; 25(10): 1883-90.
 [http://dx.doi.org/10.1016/j.drudis.2020.07.011] [PMID: 32712312]

[442]
Kumar A, Khan IA, Koul S, et al. Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus. J Antimicrob Chemother  2008; 61(6): 1270-6.
 [http://dx.doi.org/10.1093/jac/dkn088] [PMID: 18334493]

[443]
Sudano Roccaro A, Blanco AR, Giuliano F, Rusciano D, Enea V. Epigallocatechin-gallate enhances the activity of tetracycline in staphylococci by inhibiting its efflux from bacterial cells. Antimicrob Agents Chemother  2004; 48(6): 1968-73.
 [http://dx.doi.org/10.1128/AAC.48.6.1968-1973.2004] [PMID: 15155186]

[444]
Kalia NP, Mahajan P, Mehra R, et al. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus. J Antimicrob Chemother  2012; 67(10): 2401-8.
 [http://dx.doi.org/10.1093/jac/dks232] [PMID: 22807321]

[445]
Han Y, Tan TMC, Lim LY. Effects of capsaicin on P-gp function and expression in Caco-2 cells. Biochem Pharmacol  2006; 71(12): 1727-34.
 [http://dx.doi.org/10.1016/j.bcp.2006.03.024] [PMID: 16674925]

[446]
Gibbons S, Moser E, Kaatz GW. Catechin gallates inhibit multidrug resistance (MDR) in Staphylococcus aureus. Planta Med  2004; 70(12): 1240-2.
 [http://dx.doi.org/10.1055/s-2004-835860] [PMID: 15643566]

[447]
Chan BCL, Ip M, Lau CBS, et al. Synergistic effects of baicalein with ciprofloxacin against NorA over-expressed methicillin-resistant Staphylococcus aureus (MRSA) and inhibition of MRSA pyruvate kinase. J Ethnopharmacol  2011; 137(1): 767-73.
 [http://dx.doi.org/10.1016/j.jep.2011.06.039] [PMID: 21782012]

[448]
Fujita M, Shiota S, Kuroda T, et al. Remarkable synergies between baicalein and tetracycline, and baicalein and β-lactams against methicillin-resistant Staphylococcus aureus. Microbiol Immunol  2005; 49(4): 391-6.
 [http://dx.doi.org/10.1111/j.1348-0421.2005.tb03732.x] [PMID: 15840965]

[449]
Lorenzi V, Muselli A, Bernardini AF, et al. Geraniol restores antibiotic activities against multidrug-resistant isolates from gram-negative species. Antimicrob Agents Chemother  2009; 53(5): 2209-11.
 [http://dx.doi.org/10.1128/AAC.00919-08] [PMID: 19258278]

[450]
Chevalier J, Atifi S, Eyraud A, Mahamoud A, Barbe J, Pagès JM. New pyridoquinoline derivatives as potential inhibitors of the fluoroquinolone efflux pump in resistant Enterobacter aerogenes strains. J Med Chem  2001; 44(23): 4023-6.
 [http://dx.doi.org/10.1021/jm010911z] [PMID: 11689091]

[451]
German N, Wei P, Kaatz GW, Kerns RJ. Synthesis and evaluation of fluoroquinolone derivatives as substrate-based inhibitors of bacterial efflux pumps. Eur J Med Chem  2008; 43(11): 2453-63.
 [http://dx.doi.org/10.1016/j.ejmech.2008.01.042] [PMID: 18358571]

[452]
Bhardwaj RK, Glaeser H, Becquemont L, Klotz U, Gupta SK, Fromm MF. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther  2002; 302(2): 645-50.
 [http://dx.doi.org/10.1124/jpet.102.034728] [PMID: 12130727]

[453]
Khan IA, Mirza ZM, Kumar A, Verma V, Qazi GN. Piperine, a phytochemical potentiator of ciprofloxacin against Staphylococcus aureus. Antimicrob Agents Chemother  2006; 50(2): 810-2.
 [http://dx.doi.org/10.1128/AAC.50.2.810-812.2006] [PMID: 16436753]

[454]
Mirza ZM, Kumar A, Kalia NP, Zargar A, Khan IA. Piperine as an inhibitor of the MdeA efflux pump of Staphylococcus aureus. J Med Microbiol  2011; 60(10): 1472-8.
 [http://dx.doi.org/10.1099/jmm.0.033167-0] [PMID: 21680766]

[455]
Markham PN, Westhaus E, Klyachko K, Johnson ME, Neyfakh AA. Multiple novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus. Antimicrob Agents Chemother  1999; 43(10): 2404-8.
 [http://dx.doi.org/10.1128/AAC.43.10.2404] [PMID: 10508015]

[456]
Samosorn S, Bremner JB, Ball A, Lewis K. Synthesis of functionalised 2-Aryl-5-Nitro-1H-indoles and their activity as bacterial nora efflux pump inhibitors. Bioorganic Med Chem  2006; 14(3): 857-65.
 [http://dx.doi.org/10.1016/j.bmc.2005.09.019]

[457]
Aeschlimann JR, Dresser LD, Kaatz GW, Rybak MJ. Effects of NorA inhibitors on in vitro antibacterial activities and postantibiotic effects of levofloxacin, ciprofloxacin, and norfloxacin in genetically related strains of Staphylococcus aureus. Antimicrob Agents Chemother  1999; 43(2): 335-40.
 [http://dx.doi.org/10.1128/AAC.43.2.335]

[458]
Gibbons S, Udo EE. The effect of reserpine, a modulator of multidrug efflux pumps, on the in vitro activity of tetracycline against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) possessing the Tet(K) determinant. Phytother Res  2000; 14(2): 139-40.
 [http://dx.doi.org/10.1002/(SICI)1099-1573(200003)14:2<139::AID-PTR608>3.0.CO;2-8]

[459]
Kaatz G, Moudgal VV, Seo SM, Hansen JB, Kristiansen JE. Phenylpiperidine selective serotonin reuptake inhibitors interfere with multi-drug efflux pump activity in Staphylococcus aureus. Int J Antimicrob Agents  2003; 22(3): 254-61.
 [http://dx.doi.org/10.1016/S0924-8579(03)00220-6] [PMID: 13678830]

[460]
Sabatini S, Gosetto F, Serritella S, et al. Pyrazolo[4,3-c][1,2]benzothiazines 5,5-dioxide: A promising new class of Staphylococcus aureus NorA efflux pump inhibitors. J Med Chem  2012; 55(7): 3568-72.
 [http://dx.doi.org/10.1021/jm201446h] [PMID: 22432682]

[461]
Holler JG, Christensen SB, Slotved HC, et al. Novel inhibitory activity of the Staphylococcus aureus NorA efflux pump by a kaempferol rhamnoside isolated from Persea lingue Nees. J Antimicrob Chemother  2012; 67(5): 1138-44.
 [http://dx.doi.org/10.1093/jac/dks005] [PMID: 22311936]

[462]
Neyfakh AA, Bidnenko VE, Lan Bo Chen. Efflux-mediated multidrug resistance in Bacillus subtilis: Similarities and dissimilarities with the mammalian system. Proc Natl Acad Sci USA  1991; 88(11): 4781-5.

[463]
Gibbons S, Oluwatuyi M, Kaatz GW. A novel inhibitor of multidrug efflux pumps in Staphylococcus aureus. J Antimicrob Chemother  2003; 51(1): 13-7.
 [http://dx.doi.org/10.1093/jac/dkg044] [PMID: 12493782]

[464]
Guay GG, Tuckman M, McNicholas P, Rothstein DM. The tet(K) gene from Staphylococcus aureus mediates the transport of potassium in Escherichia coli. J Bacteriol  1993; 175(15): 4927-9.
 [http://dx.doi.org/10.1128/jb.175.15.4927-4929.1993] [PMID: 8335648]

[465]
Chovanová R, Mezovská J. The inhibition the Tet(K) efflux pump of tetracycline resistant Staphylococcus epidermidis by essential oils from three salvia species. Lett Appl Microbiol 2015  2015; 61(1): 58-62.
 [http://dx.doi.org/10.1111/lam.12424]

[466]
Limaverde PW, Campina FF, da Cunha FAB, Crispim FD, Figueredo FG, Lima LF. Datiane de M. Oliveira-Tintino, C.; de Matos, Y.M.L.S.; Morais-Braga, M.F.B.; Menezes, I.R.A.; Balbino, V.Q.; Coutinho, H.D.M.; Siqueira-Júnior, J.P.; Almeida, J.R.G.S.; Tintino, S.R. Inhibition of the TetK efflux-pump by the essential oil of Chenopodium ambrosioides L. and α-Terpinene against Staphylococcus aureus IS-58. Food Chem Toxicol 2017.

[467]
Witek K, Latacz G, Kaczor A, et al. Phenylpiperazine 5,5-dimethylhydantoin derivatives as first synthetic inhibitors of Msr(A) efflux pump in Staphylococcus epidermidis. Molecules  2020; 25(17): 3788.
 [http://dx.doi.org/10.3390/molecules25173788]

[468]
Kaatz GW, Moudgal VV, Seo SM. Identification and characterization of a novel efflux-related multidrug resistance phenotype in Staphylococcus aureus. J Antimicrob Chemother  2002; 50(6): 833-8.
 [http://dx.doi.org/10.1093/jac/dkf224] [PMID: 12461001]

[469]
Moriyama Y, Hiasa M, Matsumoto T, Omote H. Multidrug and toxic compound extrusion (MATE)-type proteins as anchor transporters for the excretion of metabolic waste products and xenobiotics. Xenobiotica  2008; 38(7-8): 1107-18.
 [http://dx.doi.org/10.1080/00498250701883753] [PMID: 18668441]

[470]
Omote H, Hiasa M, Matsumoto T, Otsuka M, Moriyama Y. The MATE proteins as fundamental transporters of metabolic and xenobiotic organic cations. Trends Pharmacol Sci  2006; 27(11): 587-93.
 [http://dx.doi.org/10.1016/j.tips.2006.09.001] [PMID: 16996621]

[471]
Tsukagoshi N, Aono R. Entry into and release of solvents by Escherichia coli in an organic-aqueous two-liquid-phase system and substrate specificity of the AcrAB-TolC solvent-extruding pump. J Bacteriol  2000; 182(17): 4803-10.
 [http://dx.doi.org/10.1128/JB.182.17.4803-4810.2000] [PMID: 10940021]

[472]
White DG, Goldman JD, Demple B, Levy SB. Role of the acrAB locus in organic solvent tolerance mediated by expression of marA, soxS, or robA in Escherichia coli. J Bacteriol  1997; 179(19): 6122-6.
 [http://dx.doi.org/10.1128/jb.179.19.6122-6126.1997] [PMID: 9324261]

[473]
Nasie I, Steiner-Mordoch S, Schuldiner S. New substrates on the block: Clinically relevant resistances for EmrE and homologues. J Bacteriol  2012; 194(24): 6766-70.
 [http://dx.doi.org/10.1128/JB.01318-12] [PMID: 23042996]

[474]
Dean CR, Visalli MA, Projan SJ, Sum PE, Bradford PA. Efflux-mediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob Agents Chemother  2003; 47(3): 972-8.
 [http://dx.doi.org/10.1128/AAC.47.3.972-978.2003] [PMID: 12604529]

[475]
Köhler T, Kok M, Michea-Hamzehpour M, et al. Multidrug efflux in intrinsic resistance to trimethoprim and sulfamethoxazole in Pseudomonas aeruginosa. Antimicrob Agents Chemother  1996; 40(10): 2288-90.
 [http://dx.doi.org/10.1128/AAC.40.10.2288] [PMID: 9036831]

[476]
Morita Y, Komori Y, Mima T, Kuroda T, Mizushima T, Tsuchiya T. Construction of a series of mutants lacking all of the four major mex operons for multidrug efflux pumps or possessing each one of the operons from Pseudomonas aeruginosa PAO1: MexCD-OprJ is an inducible pump. FEMS Microbiol Lett  2001; 202(1): 139-43.
 [http://dx.doi.org/10.1111/j.1574-6968.2001.tb10794.x] [PMID: 11506922]

[477]
Kaatz GW, Moudgal VV, Seo SM, Kristiansen JE. Phenothiazines and thioxanthenes inhibit multidrug efflux pump activity in Staphylococcus aureus. Antimicrob Agents Chemother  2003; 47(2): 719-26.
 [http://dx.doi.org/10.1128/AAC.47.2.719-726.2003] [PMID: 12543683]

[478]
Moreira MAS, Rodrigues PPCF, Tomaz RS, Moraes CA. Multidrug efflux systems in Escherichia coli and Enterobacter cloacae obtained from wholesome broiler carcasses. Braz J Microbiol  2009; 40(2): 241-7.
 [http://dx.doi.org/10.1590/S1517-83822009000200007] [PMID: 24031352]

[479]
Martins A, Spengler G, Martins M, et al. Physiological characterisation of the efflux pump system of antibiotic-susceptible and multi-drug-resistant Enterobacter aerogenes. Int J Antimicrob Agents  2010; 36(4): 313-8.
 [http://dx.doi.org/10.1016/j.ijantimicag.2010.06.036] [PMID: 20688487]

[480]
Joux F, Lebaron P. Use of fluorescent probes to assess physiological functions of bacteriaat single-cell level. Microbes Infect  2000; 2(12): 1523-35.
 [http://dx.doi.org/10.1016/S1286-4579(00)01307-1] [PMID: 11099939]

[481]
Olmsted J III, Kearns DR. Mechanism of ethidium bromide fluorescence enhancement on binding to nucleic acids. Biochemistry  1977; 16(16): 3647-54.
 [http://dx.doi.org/10.1021/bi00635a022] [PMID: 889813]

[482]
Martins M, Santos B, Martins A, et al. An instrument-free method for the demonstration of efflux pump activity of bacteria. In Vivo  2006; 20(5): 657-4.
 [PMID: 17091774]

[483]
Viveiros M, Dupont M, Rodrigues L, et al. Antibiotic stress, genetic response and altered permeability of E. coli. PLoS One  2007; 2(4): e365.
 [http://dx.doi.org/10.1371/journal.pone.0000365] [PMID: 17426813]

[484]
Davin-Regli A, Bolla JM, James C, et al. Membrane permeability and regulation of drug “influx and efflux” in enterobacterial pathogens. Curr Drug Targets  2008; 9(9): 750-9.
 [http://dx.doi.org/10.2174/138945008785747824]

[485]
Amaral L, Cerca P, Spengler G, et al. Ethidium bromide efflux by salmonella: Modulation by metabolic Energy, PH, Ions and phenothia-zines. Int J Antimicrob Agents  2011; 38(2): 140-5.
 [http://dx.doi.org/10.1016/j.ijantimicag.2011.03.014]

[486]
Amaral L, Fanning S, Pagés JM. Efflux Pumps of gram-negative bacteria: Genetic responses to stress and the modulation of their activity by ph, inhibitors, and phenothiazines. Adv Enzymol Relat Areas Mol Biol 2010.
 [PMID: 21692367]

[487]
Viveiros M, Martins M, Couto I, et al. New methods for the identification of efflux mediated MDR bacteria, genetic assessment of regulators and efflux pump constituents, characterization of efflux systems and screening for inhibitors of efflux pumps. Curr Drug Targets  2008; 9(9): 760-78.
 [http://dx.doi.org/10.2174/138945008785747734] [PMID: 18781922]

[488]
Jernaes MW, Steen HB. Staining of Escherichia coli for flow cytometry: Influx and efflux of ethidium bromide. Cytometry  1994; 17(4): 302-9.
 [http://dx.doi.org/10.1002/cyto.990170405] [PMID: 7875037]

[489]
Sabnis RW. Handbook of Biological Dyes and Stains: Synthesisand Industrial Applications. 2010.

[490]
Paixão L, Rodrigues L, Couto I, et al. Fluorometric determination of ethidium bromide efflux kinetics in Escherichia coli. J Biol Eng  2009; 3(1): 18.
 [http://dx.doi.org/10.1186/1754-1611-3-18] [PMID: 19835592]

[491]
Viveiros M, Martins A, Paixão L, et al. Demonstration of intrinsic efflux activity of Escherichia coli K-12 AG100 by an automated ethidium bromide method. Int J Antimicrob Agents  2008; 31(5): 458-62.
 [http://dx.doi.org/10.1016/j.ijantimicag.2007.12.015] [PMID: 18343640]

[492]
Blair JMA, Piddock LJV. How to Measure export via bacterial multidrug resistance efflux pumps. MBio  2016; 7(4): e00840-16.
 [http://dx.doi.org/10.1128/mBio.00840-16] [PMID: 27381291]

[493]
Waring MJ. Structural requirements for the binding of ethidium to nucleic acids. Biochim Biophys Acta  1966; 114(2): 234-44.
 [http://dx.doi.org/10.1016/0005-2787(66)90305-4]

[494]
Lepecq JB, Paoletti C. A fluorescent complex between ethidium bromide and nucleic acids. J Mol Biol  1967; 27(1): 87-106.
 [http://dx.doi.org/10.1016/0022-2836(67)90353-1] [PMID: 6033613]

[495]
Wang JC. Variation of the average rotation angle of the DNA helix and the superhelical turns of covalently closed cyclic λ DNA. J Mol Biol  1969; 43(1): 25-39.
 [http://dx.doi.org/10.1016/0022-2836(69)90076-X] [PMID: 4897794]

[496]
Olavarrieta L, Martínez-Robles ML, Sogo JM, et al. Supercoiling, knotting and replication fork reversal in partially replicated plasmids. Nucleic Acids Res  2002; 30(3): 656-66.
 [http://dx.doi.org/10.1093/nar/30.3.656] [PMID: 11809877]

[497]
Bauer W, Vinograd J. The interaction of closed circular DNA with intercalative dyes. J Mol Biol  1968; 33(1): 141-71.
 [http://dx.doi.org/10.1016/0022-2836(68)90286-6] [PMID: 4296517]

[498]
Erard M, Das GC, de Murcia G, et al. Ethidium bromide binding to core particle: Comparison with native chromatin. Nucleic Acids Res  1979; 6(10): 3231-54.
 [http://dx.doi.org/10.1093/nar/6.10.3231] [PMID: 482127]

[499]
Bouanchaud DH, Scavizzi MR, Chabbert YA. Elimination by ethidium bromide of antibiotic resistance in enterobacteria and staphylococci. J Gen Microbiol  1968; 54(3): 417-25.
 [http://dx.doi.org/10.1099/00221287-54-3-417] [PMID: 4885039]

[500]
Seeger M, Diederichs K, Eicher T, et al. The AcrB efflux pump: Conformational cycling and peristalsis lead to multidrug resistance. Curr Drug Targets  2008; 9(9): 729-49.
 [http://dx.doi.org/10.2174/138945008785747789] [PMID: 18781920]

[501]
Sharples D, Brown JR. Correlation of the base specificity of DNA intercalating ligands with their physico-chemical properties. FEBS Lett  1976; 69(1-2): 37-40.
 [http://dx.doi.org/10.1016/0014-5793(76)80648-5] [PMID: 1033085]

[502]
Martins M, McCusker MP, Viveiros M, et al. A simple method for assessment of mdr bacteria for over-expressed efflux pumps. Open Microbiol J  2013; 7(1): 72-82.
 [http://dx.doi.org/10.2174/1874285801307010072] [PMID: 23589748]

[503]
Piddock LJV, Jin YF, Ricci V, Asuquo AE. Quinolone accumulation by Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. J Antimicrob Chemother  1999; 43(1): 61-70.
 [http://dx.doi.org/10.1093/jac/43.1.61] [PMID: 10381102]

[504]
Mortimer PGS, Piddock LJV. A comparison of methods used for measuring the accumulation of quinolones by Enterobacteriaceae, Pseudomonas aeruginosa and Staphylococcus aureus. J Antimicrob Chemother  1991; 28(5): 639-53.
 [http://dx.doi.org/10.1093/jac/28.5.639] [PMID: 1663928]

[505]
Reissert A. On di-γ‐amidopropyl) acetic acid (Diamino.1.7.Heptanemethyl Acid.4) and its internal condensation product, the octohydro.1.8.Naphtyridine. Reports of the Dtsch Chem Society 1893.

[506]
Bobrański B, Sucharda E. On a synthesis of 1.5-naphthyridine. Reports of the German Chem Society (AB Ser 1927) 

[507]
Koller G. On 1.8-Naphthyridine. Reports by Dtsch Chem Society (AB Ser 1927).

[508]
Koller G. On 1.8-Naphthyridine and its derivatives (Preliminary communication). Reports of the Dtsch Chem Gesellschaft (AB Ser 1927).

[509]
Koller G. On a Synthesis of derivatives of 1.8-naphthyridine. Reports of the Dtsch Chem Gesellschaft (AB Ser1927).

[510]
Bachand B. Antiviral Methods Using [1, 8] Naphthyridine Derivatives. US patent 6,340,690, 2002.

[511]
Domagala JM, Mich TF, Nichols JB. Naphthyridine antibacterial agents. US patent 5,281,612, 1994.

[512]
Litvinov VP. Chemistry and biological activities of 1,8-naphthyridines. Russ Chem Rev  2004; 73(7): 637-70.
 [http://dx.doi.org/10.1070/RC2004v073n07ABEH000856]

[513]
Litvinov VP, Roman SV, Dyachenko VD. Naphthyridines. Structure, physicochemical properties and general methods of synthesis. Russ Chem Rev  2000; 69(3): 201-20.
 [http://dx.doi.org/10.1070/RC2000v069n03ABEH000553]

[514]
Srivastava SK, Jaggi M, Singh AT, et al. Anticancer and anti-inflammatory activities of 1,8-Naphthyridine-3-Carboxamide derivatives. Bioorganic Med Chem Lett  2007; 17(23): 6660-4.

[515]
Guinea J, Gargallo-Viola D, Robert M, et al. E-4695, a new C-7 azetidinyl fluoronaphthyridine with enhanced activity against gram-positive and anaerobic pathogens. Antimicrob Agents Chemother  1995; 39(2): 413-21.
 [http://dx.doi.org/10.1128/AAC.39.2.413] [PMID: 7726507]

[516]
Nakamura S, Nakata K, Katae H, et al. Activity of AT-2266 compared with those of norfloxacin, pipemidic acid, nalidixic acid, and gentamicin against various experimental infections in mice. Antimicrob Agents Chemother  1983; 23(5): 742-9.
 [http://dx.doi.org/10.1128/AAC.23.5.742] [PMID: 6223579]

[517]
Matsumoto J, Miyamoto T, Minamida A, Nishimura Y, Egawa H, Nishimura H. 1,4-Dihydro-4-oxopyridinecarboxylic acids as antibacterial agents. 2. Synthesis and structure-activity relationships of 1,6,7-trisubstituted 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids, including enoxacin, a new antibacterial agent. J Med Chem  1984; 27(3): 292-301.
 [http://dx.doi.org/10.1021/jm00369a011] [PMID: 6422043]

[518]
Nakamura S, Minami A, Katae H, et al. In vitro antibacterial properties of AT-2266, a new pyridonecarboxylic acid. Antimicrob Agents Chemother  1983; 23(5): 641-8.
 [http://dx.doi.org/10.1128/AAC.23.5.641] [PMID: 6575721]

[519]
Yun HJ, Min YH, Lim JA, et al. In vitro and in vivo antibacterial activities of DW286, a new fluoronaphthyridone antibiotic. Antimicrob Agents Chemother  2002; 46(9): 3071-4.
 [http://dx.doi.org/10.1128/AAC.46.9.3071-3074.2002] [PMID: 12183275]

[520]
Kim EJ, Shin WH. General pharmacology of DW-286a, a new fluoronaphthyridone antibiotic: Effects on central nervous, cardiovascular, and respiratory systems. Biol Pharm Bull  2004; 27(5): 641-6.
 [http://dx.doi.org/10.1248/bpb.27.641] [PMID: 15133237]

[521]
Huang X, Chen D, Wu N, Zhang A, Jia Z, Li X. The synthesis and biological evaluation of a novel series of C7 non-basic substituted fluoroquinolones as antibacterial agents. 2009; 19(15): 4130-3.
 [http://dx.doi.org/10.1016/j.bmcl.2009.06.006]

[522]
Huang X, Zhang A, Chen D, Jia Z, Li X. 4-Substituted 4-(1H-1,2,3-Triazol-1-Yl)Piperidine: Novel C7 moieties of fluoroquinolones as antibacterial agents. Bioorganic Med Chem Lett  2010; 20(9): 2859-63.

[523]
Kondo H, Taguchi M, Inoue Y, Sakamoto F, Tsukamoto G. Synthesis and Antibacterial Activity of Thiazolo-, Oxazolo-, and Imidazolo[3,2-a][l,8]Naphthyridinecarboxylic Acids. J Med Chem 1990.

[524]
Ozaki M, Segawa J, Kitano M, et al. Structure-antibacterial activity and cytotoxicity relationships of thiazolo and thiazetoquinolone de-rivatives. Biol Pharm Bull  1996; 19(11): 1457-62.
 [http://dx.doi.org/10.1248/bpb.19.1457] [PMID: 8951164]

[525]
Tani J, Mushika Y, Yamaguchi T. Studies on biologically active halogenated compounds. IV. Synthesis and antibacterial activity of fluorinated quinoline derivatives. Chem Pharm Bull  1982; 30(10): 3530-43.

[526]
Suzuki N. Synthesis of Antimicrobial Agents. V. Synthesis and antimicrobial activities of some heterocyclic condensed 1,8-naphthyridine derivatives. Chem Pharm Bull  1980; 28(3): 761-8.

[527]
Hayakawa I, Suzuki N, Suzuki K, Tanaka Y. Synthesis of antimicrobial agents. VI. Studies on the synthesis of furo(3,2-b)(1,8)naphthyridine derivatives. Chem Pharm Bull  1984; 32(12): 4914-22.
 [http://dx.doi.org/10.1248/cpb.32.4914]

[528]
Suzuki N, Tanaka Y, Dohmori R. Synthesis of antimicrobial agents. IV. Synthesis and antimicrobial activities of imidazo[4,5-b][1,8]naphthyridine derivafives. Chem Pharm Bull  1980; 28(1): 235-44.
 [http://dx.doi.org/10.1248/cpb.28.235] [PMID: 7363372]

[529]
Mills DA, Fekrazad HM, Verschraegen CF. SNS-595, a naphthyridine cell cycle inhibitor and stimulator of apoptosis for the treatment of cancers. Curr Opin Investig Drugs  2008; 9(6): 647-57.
 [PMID: 18516764]

[530]
Abbas JA, Stuart RK. Vosaroxin: A novel antineoplastic quinolone. Expert Opin Investig Drugs  2012; 21(8): 1223-33.
 [http://dx.doi.org/10.1517/13543784.2012.699038] [PMID: 22724917]

[531]
Freeman C, Keane N, Swords R, Giles F. Vosaroxin: A new valuable tool with the potential to replace anthracyclines in the treatment of AML? Expert Opin Pharmacother  2013; 14(10): 1417-27.
 [http://dx.doi.org/10.1517/14656566.2013.799138] [PMID: 23688047]

[532]
Hawtin RE, Stockett DE, Wong OK, Lundin C, Helleday T, Fox JA. Homologous recombination repair is essential for repair of vosaroxin-induced DNA double-strand breaks. Oncotarget  2010; 1(7): 606-19.
 [http://dx.doi.org/10.18632/oncotarget.195] [PMID: 21317456]

[533]
Hoch U, Lynch J, Sato Y, et al. Voreloxin, formerly SNS-595, has potent activity against a broad panel of cancer cell lines and in vivo tumor models. Cancer Chemother Pharmacol  2009; 64(1): 53-65.
 [http://dx.doi.org/10.1007/s00280-008-0850-3] [PMID: 18931998]

[534]
Argiropoulos G, Bates MRM, Cherubim P, et al. Cytotoxic and DNA binding properties of aminoalkyl derivatives of di- and triazaphenanthrenes. Anticancer Drug Des  1992; 7(4): 285-96.
 [PMID: 1510798]

[535]
Tsuzuki Y, Tomita K, Sato Y, Kashimoto S, Chiba K. Synthesis and structure-activity relationships of 3-Substituted 1,4-Dihydro-4-Oxo-1-(2-Thiazolyl)-1,8-Naphthyridines as novel antitumor agents. Bioorganic Med Chem Lett  2004; 14(12): 3189-93.
 [http://dx.doi.org/10.1016/j.bmcl.2004.04.011]

[536]
Banti I, Nencetti S, Orlandini E, Lapucci A, Breschi MC, Fogli S. Synthesis and in-vitro antitumour activity of new naphthyridine derivatives on human pancreatic cancer cells. J Pharm Pharmacol  2010; 61(8): 1057-66.
 [http://dx.doi.org/10.1211/jpp.61.08.0010] [PMID: 19703350]

[537]
Hwang HJ, Kang YJ, Hossain MA, et al. Novel dihydrobenzofuro[4,5-b][1,8]naphthyridin-6-one derivative, MHY-449, induces apoptosis and cell cycle arrest in HCT116 human colon cancer cells. Int J Oncol  2012; 41(6): 2057-64.
 [http://dx.doi.org/10.3892/ijo.2012.1659] [PMID: 23064444]

[538]
Hwang YJ, Chung ML, Sohn UD. Cytotoxicity and structure-activity relationships of naphthyridine derivatives in human cervical cancer, leukemia, and prostate cancer. Korean J Physiol Pharmacol  2013; 17(6): 517-23.
 [http://dx.doi.org/10.4196/kjpp.2013.17.6.517]

[539]
Elansary AK, Moneer AA, Kadry HH, Gedawy EM. Synthesis and Antitumour Activity of Certain Pyrido[2,3- d] Pyrimidine and 1,8-naphthyridine Derivatives. J Chem Res  2014; 38(3): 147-53.
 [http://dx.doi.org/10.3184/174751914X13910886393992]

[540]
Gao LZ, Li T, Yu XS, Huang WL, Zhao H, Hu GQ. [Design, synthesis, antibacterial and anti-cell proliferation activities of [1,2,4]triazino[3,4-h] [1,8]naphthyridine-8-one-7-carboxylic acid derivatives]. Yao Xue Xue Bao 2015.

[541]
Kumar V, Jaggi M, Singh AT, et al. 1,8-Naphthyridine-3-carboxamide derivatives with anticancer and anti-inflammatory activity. Eur J Med Chem  2009; 44(8): 3356-62.
 [http://dx.doi.org/10.1016/j.ejmech.2009.03.015] [PMID: 19361894]

[542]
Fu L, Feng X, Wang JJ, et al. Efficient synthesis and evaluation of antitumor activities of novel functionalized 1,8-naphthyridine derivatives. ACS Comb Sci  2015; 17(1): 24-31.
 [http://dx.doi.org/10.1021/co500120b] [PMID: 25412896]

[543]
Oh YS, Cho SH. Syntheses of new pyridonecarboxylic acid derivatives containing 1- or 2-naohthyl substituents at N-1 and their anti-HIV-RT activities. J Heterocycl Chem 1998.

[544]
Williams PD, Staas DD, Venkatraman S, et al. Potent and selective HIV-1 ribonuclease h inhibitors based on a 1-Hydroxy-1,8-Naphthyridin-2(1H)-one scaffold. Bioorganic Med Chem Lett  2010; 20(22): 6754-7.
 [http://dx.doi.org/10.1016/j.bmcl.2010.08.135]

[545]
Kreutner W, Sherwood J, Sehring S, et al. Antiallergy activity of Sch 37224, a new inhibitor of leukotriene formation. J Pharmacol Exp Ther  1988; 247(3): 997-1003.
 [PMID: 2462630]

[546]
Sherlock MH, Kaminski JJ, Tom WC, et al. Antiallergy agents. 1. Substituted 1,8-naphthyridin-2(1H)-ones as inhibitors of SRS-A re-lease. J Med Chem  1988; 31(11): 2108-21.
 [http://dx.doi.org/10.1021/jm00119a010] [PMID: 2903244]

[547]
Kuo SC, Tsai SY, Li HT, Wu CH, Ishii K, Nakamura H. Studies on Heterocyclic Compounds. IX.1) Synthesis and antiallergic activity of Furo[2,3-b][1,8]Naphthyridine-3,4(2H,9H)-Diones and 4H-Furo[2,3-d]Pyrido[1,2-a]-Pyrimidine-3,4(2H)-Diones. Chem Pharm Bull  1988; 36(11): 4403-7.

[548]
Hutchinson JH, Halczenko W, Brashear KM, et al. Nonpeptide Avβ3 antagonists. 8. In vitro and in vivo evaluation of a potent Avβ3 antagonist for the prevention and treatment of osteoporosis. J Med Chem  2003; 46(22): 4790-8.
 [http://dx.doi.org/10.1021/jm030306r]

[549]
Raboisson P, DesJarlais RL, Reed R, et al. Identification of novel short chain 4-substituted indoles as potent αvβ3 antagonist using structure-based drug design. Eur J Med Chem  2007; 42(3): 334-43.
 [http://dx.doi.org/10.1016/j.ejmech.2006.10.015]

[550]
Coleman PJ, Brashear KM, Askew BC, et al. Nonpeptide α v β 3 Antagonists. Part 11: Discovery and preclinical evaluation of potent α v β 3 antagonists for the prevention and treatment of osteoporosis. J Med Chem  2004; 47(20): 4829-37.
 [http://dx.doi.org/10.1021/jm049874c] [PMID: 15369386]

[551]
Suzuki F, Kuroda T, Kawakita T, et al. New Bronchodilators. 3. Imidazo[4,5-c][1,8]Naphthyridin-4(5H)-Ones. J Med Chem  1992; 35(26): 4866-74.
 [http://dx.doi.org/10.1021/jm00104a013]

[552]
Santilli AA, Scotese AC, Bauer RF, Bell SC. 2-Oxo-1,8-naphthyridine-3-carboxylic acid derivatives with potent gastric antisecretory properties. J Med Chem  1987; 30(12): 2270-7.
 [http://dx.doi.org/10.1021/jm00395a015] [PMID: 3681897]

[553]
Dedieu-Chaufour C, Hertz F, Caussade F, Cloarec A. Pharmacological profile of up 5145-52, 1 an original antiulcer and antisecretory agent. J Pharmacol Exp Ther 1991.
 [PMID: 1656018]

[554]
Adams JT, Bradsher CK, Breslow DS, Amore ST, Hauser CR. Synthesis of antimalarials; synthesis of certain 1,5- and 1,8-naphthyridine derivatives. J Am Chem Soc  1946; 68(7): 1317-9.
 [http://dx.doi.org/10.1021/ja01211a064] [PMID: 20990995]

[555]
Barlin G, Tan W. Potential antimalarials. I. 1,8-naphthyridines. Aust J Chem  1984; 37(5): 1065.
 [http://dx.doi.org/10.1071/CH9841065]

[556]
Barreiro EJ, Camara CA, Verli H, et al. Design, synthesis, and pharmacological profile of novel fused pyrazolo[4,3-d]pyridine and pyrazolo[3,4-b][1,8]naphthyridine isosteres: A new class of potent and selective acetylcholinesterase inhibitors. J Med Chem  2003; 46(7): 1144-52.
 [http://dx.doi.org/10.1021/jm020391n] [PMID: 12646025]

[557]
Gautam BK, Jindal A, Dhar AK, Mahesh R. Antidepressant-like activity of 2-(4-phenylpiperazin-1-yl)-1, 8-naphthyridine-3-carboxylic acid (7a), a 5-HT3 receptor antagonist in behaviour based rodent models: Evidence for the involvement of serotonergic system. Pharmacol Biochem Behav  2013; 109: 91-7.
 [http://dx.doi.org/10.1016/j.pbb.2013.05.006] [PMID: 23680574]

[558]
Mahesh R, Dhar AK, Jindal A, Bhatt S. Design, synthesis and evaluation of antidepressant activity of novel 2-methoxy 1, 8 naphthyridine 3-carboxamides as 5-HT3 receptor antagonists. Chem Biol Drug Des  2014; 83(5): 583-91.
 [http://dx.doi.org/10.1111/cbdd.12271] [PMID: 24330585]

[559]
Dhar AK, Mahesh R, Jindal A, Devadoss T, Bhatt S. Design, synthesis, and pharmacological evaluation of novel 2-(4-substituted piperazin-1-yl)1, 8 naphthyridine 3-carboxylic acids as 5-HT3 receptor antagonists for the management of depression. Chem Biol Drug Des  2014; 84(6): 721-31.
 [http://dx.doi.org/10.1111/cbdd.12370] [PMID: 24903617]

[560]
Leonard JT, Gangadhar R, Gnanasam SK, Ramachandran S, Saravanan M, Sridhar SK. Synthesis and pharmacological activities of 1,8-naphthyridine derivatives. Biol Pharm Bull  2002; 25(6): 798-802.
 [http://dx.doi.org/10.1248/bpb.25.798] [PMID: 12081151]

[561]
Ferrarini PL, Mori C, Calderone V, et al. Synthesis of 1,8-naphthyridine derivatives: Potential antihypertensive agents - Part VIII. Eur J Med Chem  1999; 34(6): 505-13.
 [http://dx.doi.org/10.1016/S0223-5234(99)80099-3]

[562]
Badawneh M, Ferrarini PL, Calderone V, et al. Synthesis and evaluation of antihypertensive activity of 1,8-naphthyridine derivatives. Part X. Eur J Med Chem  2001; 36(11-12): 925-34.
 [http://dx.doi.org/10.1016/S0223-5234(01)01277-6] [PMID: 11755235]

[563]
Ferrarini PL, Mori C, Badawneh M, et al. Unusual nitration of substituted 7-amino-1,8-naphthyridine in the synthesis of compounds with antiplatelet activity. J Heterocycl Chem  1997; 34(5): 1501-10.
 [http://dx.doi.org/10.1002/jhet.5570340520]

[564]
Ferrarini PL, Mori C, Badawneh M, et al. Synthesis and antiplatelet activity of some 3-phenyl-1,8-naphthyridine derivatives. Farmaco  2000; 55(9-10): 603-10.
 [http://dx.doi.org/10.1016/S0014-827X(00)00085-9] [PMID: 11152241]

[565]
Ferrarini PL, Badawneh M, Franconi F, et al. Synthesis and antiplatelet activity of some 2,7-di(N-cycloamino)-3-phenyl-1,8-naphthyridine derivatives. Farmaco  2001; 56(4): 311-8.
 [http://dx.doi.org/10.1016/S0014-827X(01)01075-8] [PMID: 11421260]

[566]
Anand N. Sulfonamides and Sulfones. Mechanism of Action of Antimicrobial and Antitumor Agents.  1975.
 [http://dx.doi.org/10.1007/978-3-642-46304-4_45]

[567]
Trefouel J, Nitti F, Bovet D. Action of P-aminophenylsulfamide in experimental streptococcus infections of mice and rabbits. C R Seances Soc Biol Fil 1935.

[568]
Fouts JR, Kamm JJ, Brodie BB. Enzymatic reduction of prontosil and other azo dyes. J Pharmacol Exp Ther  1957; 120(3): 291-300.

[569]
Goulian M, Bleile BM, Dickey LM, et al. Mechanism of thymineless death. Adv Exp Med Biol  1986; B(Pt B): 89-95.
 [http://dx.doi.org/10.1007/978-1-4684-1248-2_15] [PMID: 3020930]

[570]
Roland S, Ferone R, Harvey RJ, Styles VL, Morrison RW. The characteristics and significance of sulfonamides as substrates for Escherichia coli dihydropteroate synthase. J Biol Chem  1979; 254(20): 10337-45.
 [http://dx.doi.org/10.1016/S0021-9258(19)86714-5] [PMID: 385600]

[571]
Seydel JK. Sulfonamides, structure-activity relationship, and mode of action. Structural problems of the antibacterial action of 4-aminobenzoic acid (PABA) antagonists. J Pharm Sci  1968; 57(9): 1455-78.
 [http://dx.doi.org/10.1002/jps.2600570902] [PMID: 4877188]

[572]
Argyropoulou I, Geronikaki A, Vicini P, Zani F. Synthesis and biological evaluation of sulfonamide thiazole and benzothiazole derivatives as antimicrobial agents. ARKIVOC  2009; 2009(6): 89-102.
 [http://dx.doi.org/10.3998/ark.5550190.0010.611]

[573]
Woods DD. The Relation of P-Aminobenzoic acid to the mechanism of the action of sulphanilamide. Br J Exp Pathol  1940; 21: 74.

[574]
Masereel B, Thiry A, Dogne J-M, Supuran C. Anticonvulsant sulfonamides/sulfamates/sulfamides with carbonic anhydrase inhibitory activity: Drug design and mechanism of action. Curr Pharm Des  2008; 14(7): 661-71.
 [http://dx.doi.org/10.2174/138161208783877956] [PMID: 18336312]

[575]
Scozzafava A, Owa T, Mastrolorenzo A, Supuran C. Anticancer and antiviral sulfonamides. Curr Med Chem  2005; 10(11): 925-53.
 [PMID: 12678681]

[576]
casini A, Scozzafava A, Mastrolorenzo A, Supuran C. Sulfonamides and sulfonylated derivatives as anticancer agents. Curr Cancer Drug Targets  2005; (1): 55-75.

[577]
Supuran CT. Carbonic anhydrase inhibition and the management of hypoxic tumors. Metabolites  2017; 7(3): 48.
 [http://dx.doi.org/10.3390/metabo7030048] [PMID: 28926956]

[578]
Forster WG. Treatment of trachoma with sulfanilamide. Arch Ophthalmol  1939; 21(4): 577-80.

[579]
Hirschfelder M. Treatment of trachoma with sulfanilamide. Am J Ophthalmol  1939; 22(3): 299-300.
 [http://dx.doi.org/10.1016/S0002-9394(39)90817-2]

[580]
Hamre D, Rake G. Studies on Lymphogranuloma venereum; the action of some antibiotic substances and sulfonamides in vitro and in vivo upon the agents of Feline pneumonitis and Lymphogranuloma venereum. J Infect Dis  1947; 81(2): 175-90.
 [http://dx.doi.org/10.1093/infdis/81.2.175] [PMID: 20266920]

[581]
Coggeshall LT. The Selective action of sulfanilamide on the parasites of experimental malaria in monkeys in vivo and in vitro. J Exp Med  1940; 71(1): 13-20.
 [http://dx.doi.org/10.1084/jem.71.1.13] [PMID: 19870940]

[582]
Goldberger HA. The potentiation of the sulfonamides in the local therapy of wounds and surgical infections by the use of oxidants. Am J Surg  1942; 56(2): 353-74.
 [http://dx.doi.org/10.1016/S0002-9610(42)90696-2]

[583]
Sabin AB, Warren J. Therapeutic effectiveness of certain sulfonamides on infection by an intracellular protozoon (toxoplasma). Exp Biol Med  1942; 51(1): 19-23.
 [http://dx.doi.org/10.3181/00379727-51-13809]

[584]
Senekji HA. The effect of sulfanilamide and trypaflavin on cultures of Leishmania tropica. J Infect Dis  1940; 66(2): 111-2.
 [http://dx.doi.org/10.1093/infdis/66.2.111]

[585]
Rodaniche EC, Kirsner JB. The effect of sulfonamide compounds on the growth of Endamoeba histolytica in Culture. J Parasitol  1942; 28(6): 441.
 [http://dx.doi.org/10.2307/3272904]

[586]
Prandota J. Furosemide: Progress in understanding its diuretic, anti-inflammatory, and bronchodilating mechanism of action, and use in the treatment of respiratory tract diseases. Am J Ther  2002; 9(4): 317-28.
 [http://dx.doi.org/10.1097/00045391-200207000-00009] [PMID: 12115021]

[587]
Boyd AE III. Sulfonylurea receptors, ion channels, and fruit flies. Diabetes  1988; 37(7): 847-50.
 [http://dx.doi.org/10.2337/diab.37.7.847] [PMID: 2454858]

[588]
de los Ríos C, Egea J, Marco-Contelles J, et al. Synthesis, inhibitory activity of cholinesterases, and neuroprotective profile of novel 1,8-naphthyridine derivatives. J Med Chem  2010; 53(14): 5129-43.
 [http://dx.doi.org/10.1021/jm901902w] [PMID: 20575555]

[589]
Shoaib Ahmad Shah S, Rivera G, Ashfaq M. Recent Advances in medicinal chemistry of sulfonamides. rational design as antitumoral, anti-bacterial and anti-inflammatory agents. MiniReviews Med Chem  2012; 13(1): 70-86.

[590]
Araújo-Neto JB, Silva MMC, Oliveira-Tintino CDM, et al. Enhancement of antibiotic activity by 1,8-naphthyridine derivatives against multi-resistant bacterial strains. Molecules  2021; 26(23): 7400.
 [http://dx.doi.org/10.3390/molecules26237400] [PMID: 34885981]

[591]
Oliveira-Tintino CD de M, Tintino SR, Muniz DF, et al. Do 1,8-naphthyridine sulfonamides possess an inhibitory action against tet(k) and msra efflux pumps in multiresistant Staphylococcus aureus strains? Microb Pathog  2020; 147.

[592]
Oliveira-Tintino CD de M, Tintino SR, Muniz DF. Chemical synthesis, molecular docking and mepa efflux pump inhibitory effect by 1,8-naphthyridines sulfonamides. Eur J Pharm Sci  2021; 160.

[593]
Oliveira-Tintino CDM, Muniz DF, Barbosa CRS, et al. The 1,8-naphthyridines sulfonamides are NorA efflux pump inhibitors. J Glob Antimicrob Resist  2021; 24: 233-40.
 [http://dx.doi.org/10.1016/j.jgar.2020.11.027] [PMID: 33385589]

[594]
Cedraro N, Cannalire R, Astolfi A, et al. From quinoline to quinazoline-based S. aureus nora efflux pump inhibitors by coupling a focused scaffold hopping approach and a pharmacophore search. Chem Med Chem  2021; 16(19): 3044-59.
 [http://dx.doi.org/10.1002/cmdc.202100282]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1381612829666221212101501	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286
Current Pharmaceutical Design

NorA, Tet(K), MepA, and MsrA Efflux Pumps in Staphylococcus aureus, their Inhibitors and 1,8-Naphthyridine Sulfonamides

Abstract Play Pause

Related Journals

Related Books

Abstract
