Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Mechanisms of Antimicrobial Resistance: Highlights on Current Advance Methods for Detection of Drug Resistance and Current Pipeline Antitubercular Agents

Author(s): Sunnapu Prasad, Shilpa V. P., Heba S. Abbas and Muddukrishnaiah Kotakonda*

Volume 23, Issue 15, 2022

Published on: 13 May, 2022

Page: [1824 - 1836] Pages: 13

DOI: 10.2174/1389201023666220318104042

Price: $65

Abstract

Background: Sir Alexander Fleming accidentally discovered antibiotics in 1928. Antibiotics have played a significant role in treating infectious diseases. The extensive use of antibiotics has enabled the microorganisms to develop resistance against the antibiotics given, which has become a global concern. This review aims to examine some of the mechanisms behind resistance and advanced methods for detecting drug-resistant and antibacterial drugs in the clinical pipeline.

Methods: An extensive search was carried out in different databases, viz. Scopus, Embase, Cochrane, and PubMed. The keywords used in the search were antimicrobial resistance, antibiotic resistance, antimicrobial tolerance, antibiotic tolerance, and methods to reduce antimicrobial resistance. All the studies published in the English language and studies focusing on antibiotic resistance were included in the analysis.

Results: The most common mechanisms involved in antimicrobial resistance are reflux pumping, antibiotic inactivation, acquired resistance, intrinsic resistance, mutation, bio-film resistance, etc. Antibacterial medicinal products for multidrug resistance (MDR) infections are active against pathogens, which are registered in the World Health Organization (WHO) priority pathogen list (PPL).

Conclusion: Furthermore, their innovativeness was assessed by their lack of cross-resistance. Finally, novel antibacterial drugs without pre-existing inter-resistance, especially those with highresistance gram-negative bacteria and tuberculosis (TB), are understated and urgently required.

Keywords: Antimicrobial resistance, MALDI-TOF, mNGS, antibacterial agents, TB drugs pipeline, antitubercular agents.

« Previous Next »
Graphical Abstract

[1]
WHO Antimicrobial resistance (WHO Fact sheet), 2018. Available from: who.int/news-room/fact-sheets/detail/antibiotic-resistance
[2]
Laxminarayan, R.; Duse, A.; Wattal, C.; Zaidi, A.K.; Wertheim, H.F.; Sumpradit, N.; Vlieghe, E.; Hara, G.L.; Gould, I.M.; Goossens, H.; Greko, C.; So, A.D.; Bigdeli, M.; Tomson, G.; Woodhouse, W.; Ombaka, E.; Peralta, A.Q.; Qamar, F.N.; Mir, F.; Kariuki, S.; Bhutta, Z.A.; Coates, A.; Bergstrom, R.; Wright, G.D.; Brown, E.D.; Cars, O. Antibiotic resistance-the need for global solutions. Lancet Infect. Dis., 2013, 13(12), 1057-1098.
[http://dx.doi.org/10.1016/S1473-3099(13)70318-9] [PMID: 24252483]
[3]
WHO report on surveillance of antibiotic consumption: 2016-2018 early implementations ISBN 978-92-4-151488-0. Available from: Who.int/publications/i/item/9789241514880
[4]
Fair, R.J.; Tor, Y. Antibiotics and bacterial resistance in the 21st century. Perspect. Medicin. Chem., 2014, 6, 25-64.
[http://dx.doi.org/10.4137/PMC.S14459] [PMID: 25232278]
[5]
Ghosh, C.; Sarkar, P.; Issa, R.; Haldar, J. Alternatives to conventional antibiotics in the era of antimicrobial resistance. Trends Microbiol., 2019, 27(4), 323-338.
[http://dx.doi.org/10.1016/j.tim.2018.12.010] [PMID: 30683453]
[6]
Butler, M.S.; Paterson, D.L. Antibiotics in the clinical pipeline in October 2019. J. Antibiot. (Tokyo), 2020, 73(6), 329-364.
[http://dx.doi.org/10.1038/s41429-020-0291-8] [PMID: 32152527]
[7]
Brown, E.D.; Wright, G.D. Antibacterial drug discovery in the resistance era. Nature, 2016, 529(7586), 336-343.
[http://dx.doi.org/10.1038/nature17042] [PMID: 26791724]
[8]
Theuretzbacher, U.; Gottwalt, S.; Beyer, P.; Butler, M.; Czaplewski, L.; Lienhardt, C.; Moja, L.; Paul, M.; Paulin, S.; Rex, J.H.; Silver, L.L.; Spigelman, M.; Thwaites, G.E.; Paccaud, J.P.; Harbarth, S. Analysis of the clinical antibacterial and antituberculosis pipeline. Lancet Infect. Dis., 2019, 19(2), e40-e50.
[http://dx.doi.org/10.1016/S1473-3099(18)30513-9] [PMID: 30337260]
[9]
Butler, M.S.; Blaskovich, M.A.; Cooper, M.A. Antibiotics in the clinical pipeline at the end of 2015. J. Antibiot. (Tokyo), 2017, 70(1), 3-24.
[http://dx.doi.org/10.1038/ja.2016.72] [PMID: 27353164]
[10]
Czaplewski, L.; Bax, R.; Clokie, M.; Dawson, M.; Fairhead, H.; Fischetti, V.A.; Foster, S.; Gilmore, B.F.; Hancock, R.E.W.; Harper, D.; Henderson, I.R.; Hilpert, K.; Jones, B.V.; Kadioglu, A.; Knowles, D.; Ólafsdóttir, S.; Payne, D.; Projan, S.; Shaunak, S.; Silverman, J.; Thomas, C.M.; Trust, T.J.; Warn, P.; Rex, J.H. Alternatives to antibiotics-a pipeline portfolio review. Lancet Infect. Dis., 2016, 16(2), 239-251.
[http://dx.doi.org/10.1016/S1473-3099(15)00466-1] [PMID: 26795692]
[11]
Ali, J.; Rafiq, Q.A.; Ratcliffe, E. Antimicrobial resistance mechanisms and potential synthetic treatments. Future Sci. OA, 2018, 4(4), FSO290.
[http://dx.doi.org/10.4155/fsoa-2017-0109] [PMID: 29682325]
[12]
Lempens, P.; Meehan, C.J.; Vandelannoote, K.; Fissette, K.; de Rijk, P.; Van Deun, A.; Rigouts, L.; de Jong, B.C. Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations. Sci. Rep., 2018, 8(1), 3246.
[http://dx.doi.org/10.1038/s41598-018-21378-x] [PMID: 29459669]
[13]
Baljin, B.; Gurjav, U.; Tulgaa, K.; Baldan, G.; Gunchin, B.; Sandag, T.; Pfeffer, K.; Wendel, A.F.; MacKenzie, C.R. High acquisition rate of Gram-negative multi-drug resistant organism colonization during hospitalization: a perspective from a high endemic setting. Infect. Drug Resist., 2021, 14, 3919-3927.
[http://dx.doi.org/10.2147/IDR.S328139] [PMID: 34588787]
[14]
Gueimonde, M.; Sánchez, B. G de Los Reyes-Gavilán, C.; Margolles, A. Antibiotic resistance in probiotic bacteria. Front. Microbiol., 2013, 4, 202.
[http://dx.doi.org/10.3389/fmicb.2013.00202] [PMID: 23882264]
[15]
Brook, I.; Wexler, H.M.; Goldstein, E.J. Antianaerobic antimicrobials: spectrum and susceptibility testing. Clin. Microbiol. Rev., 2013, 26(3), 526-546.
[http://dx.doi.org/10.1128/CMR.00086-12] [PMID: 23824372]
[16]
Nelson, R.R. Intrinsically vancomycin-resistant gram-positive organisms: clinical relevance and implications for infection control. J. Hosp. Infect., 1999, 42(4), 275-282.
[http://dx.doi.org/10.1053/jhin.1998.0605] [PMID: 10467540]
[17]
Miller, W.R.; Munita, J.M.; Arias, C.A. Mechanisms of antibiotic resistance in enterococci. Expert Rev. Anti Infect. Ther., 2014, 12(10), 1221-1236.
[http://dx.doi.org/10.1586/14787210.2014.956092] [PMID: 25199988]
[18]
Munita, J.M.; Arias, C.A. Mechanisms of antibiotic resistance. Microbiol. Spectr., 2016, 4(2)
[http://dx.doi.org/10.1128/microbiolspec.vmbf-0016-2015] [http://dx.doi.org/10.1128/9781555819286.ch17]
[19]
Epand, R.M.; Walker, C.; Epand, R.F.; Magarvey, N.A. Molecular mechanisms of membrane targeting antibiotics. Biochim. Biophys. Acta, 2016, 1858(5), 980-987.
[http://dx.doi.org/10.1016/j.bbamem.2015.10.018] [PMID: 26514603]
[20]
Hsieh, P.C.; Siegel, S.A.; Rogers, B.; Davis, D.; Lewis, K. Bacteria lacking a multidrug pump: a sensitive tool for drug discovery. Proc. Natl. Acad. Sci. USA, 1998, 95(12), 6602-6606.
[http://dx.doi.org/10.1073/pnas.95.12.6602] [PMID: 9618458]
[21]
Nikaido, H.; Pagès, J.M. Broad-specificity efflux pumps and their role in multidrug resistance of Gram-negative bacteria. FEMS Microbiol. Rev., 2012, 36(2), 340-363.
[http://dx.doi.org/10.1111/j.1574-6976.2011.00290.x] [PMID: 21707670]
[22]
Cavallito, C.J.; Bailey, J.H.; Haskell, T.H.; McCormick, J.R.; Warner, W.F. The inactivation of antibacterial agents and their mechanism of action. J. Bacteriol., 1945, 50(1), 61-69.
[http://dx.doi.org/10.1128/jb.50.1.61-69.1945] [PMID: 16560977]
[23]
Lambert, P.A. Bacterial resistance to antibiotics: modified target sites. Adv. Drug Deliv. Rev., 2005, 57(10), 1471-1485.
[http://dx.doi.org/10.1016/j.addr.2005.04.003] [PMID: 15964098]
[24]
Schmieder, R.; Edwards, R. Insights into antibiotic resistance through metagenomic approaches. Future Microbiol., 2012, 7(1), 73-89.
[http://dx.doi.org/10.2217/fmb.11.135] [PMID: 22191448]
[25]
van Hoek, A.H.; Mevius, D.; Guerra, B.; Mullany, P.; Roberts, A.P.; Aarts, H.J. Acquired antibiotic resistance genes: an overview. Front. Microbiol., 2011, 2, 203.
[http://dx.doi.org/10.3389/fmicb.2011.00203] [PMID: 22046172]
[26]
Singh, S.; Singh, S.K.; Chowdhury, I.; Singh, R. Understanding the mechanism of bacterial biofilms resistance to antimicrobial agents. Open Microbiol. J., 2017, 11, 53-62.
[http://dx.doi.org/10.2174/1874285801711010053] [PMID: 28553416]
[27]
Zhao, X.; Yu, Z.; Ding, T. Quorum-sensing regulation of antimicrobial resistance in bacteria. Microorganisms, 2020, 8(3), 425.
[http://dx.doi.org/10.3390/microorganisms8030425] [PMID: 32192182]
[28]
Khan, Z.A.; Siddiqui, M.F.; Park, S. Current and emerging methods of antibiotic susceptibility testing. Diagnostics (Basel), 2019, 9(2), 49.
[http://dx.doi.org/10.3390/diagnostics9020049] [PMID: 31058811]
[29]
Abrar, S.; Ain, N.U.; Liaqat, H.; Hussain, S.; Rasheed, F.; Riaz, S. Distribution of blaCTX - M, blaTEM, blaSHV and blaOXA genes in Extended-spectrum-β-lactamase-producing Clinical isolates: A three-year multi-center study from Lahore, Pakistan. Antimicrob. Resist. Infect. Control, 2019, 8, 80.
[http://dx.doi.org/10.1186/s13756-019-0536-0] [PMID: 31139363]
[30]
Anjum, M.F.; Zankari, E.; Hasman, H. Molecular methods for detection of antimicrobial resistance. Microbiol. Spectr., 2017, 5(6)
[http://dx.doi.org/10.1128/microbiolspec.ARBA-0011-2017]
[31]
Frye, J.G.; Lindsey, R.L.; Rondeau, G.; Porwollik, S.; Long, F.; McClelland, M.; Jackson, C.R.; Englen, M.D.; Meinersmann, R.J.; Berrang, M.E.; Davis, J.A.; Barrett, J.B.; Turpin, J.B.; Thitaram, S.N.; Fedorka-Cray, P.J. Development of a DNA microarray to detect antimicrobial resistance genes identified in the National Center for Biotechnology Information database. Microb. Drug Resist., 2010, 16(1), 9-19.
[http://dx.doi.org/10.1089/mdr.2009.0082] [PMID: 19916789]
[32]
Vrioni, G.; Tsiamis, C.; Oikonomidis, G.; Theodoridou, K.; Kapsimali, V.; Tsakris, A. MALDI-TOF mass spectrometry technology for detecting biomarkers of antimicrobial resistance: current achievements and future perspectives. Ann. Transl. Med., 2018, 6(12), 240.
[http://dx.doi.org/10.21037/atm.2018.06.28] [PMID: 30069442]
[33]
Axelsson, C.; Rehnstam-Holm, A.S.; Nilson, B. Rapid detection of antibiotic resistance in positive blood cultures by MALDI-TOF MS and an automated and optimized MBT-ASTRA protocol for Escherichia coli and Klebsiella pneumoniae. Infect. Dis. (Lond.), 2020, 52(1), 45-53.
[http://dx.doi.org/10.1080/23744235.2019.1682658] [PMID: 31661349]
[34]
Berglund, F.; Österlund, T.; Boulund, F.; Marathe, N.P.; Larsson, D.G.J.; Kristiansson, E. Identification and reconstruction of novel anti-biotic resistance genes from metagenomes. Microbiome, 2019, 7(1), 52.
[http://dx.doi.org/10.1186/s40168-019-0670-1] [PMID: 30935407]
[35]
De, R. Metagenomics: aid to combat antimicrobial resistance in diarrhea. Gut Pathog., 2019, 11(1), 47.
[http://dx.doi.org/10.1186/s13099-019-0331-8] [PMID: 31636714]
[36]
Muddukrishnaiah, K.; Shilpa, V.P. Marine anaerobic bacterial diversity for the production of antimicrobial agents. Environ. Dis., 2017, 2(4), 99-102.
[http://dx.doi.org/10.4103/ed.ed_14_17]
[37]
Stermitz, F.R.; Lorenz, P.; Tawara, J.N.; Zenewicz, L.A.; Lewis, K. Synergy in a medicinal plant: antimicrobial action of berberine potentiated by 5′-methoxyhydnocarpin, a multidrug pump inhibitor. Proc. Natl. Acad. Sci. USA, 2000, 97(4), 1433-1437.
[http://dx.doi.org/10.1073/pnas.030540597] [PMID: 10677479]
[38]
Witting, K.; Süssmuth, R.D. Discovery of antibacterials and other bioactive compounds from microorganisms-evaluating methodologies for discovery and generation of non-ribosomal peptide antibiotics. Curr. Drug Targets, 2011, 12(11), 1547-1559.
[http://dx.doi.org/10.2174/138945011798109527] [PMID: 21561427]
[39]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod., 2007, 70(3), 461-477.
[http://dx.doi.org/10.1021/np068054v] [PMID: 17309302]
[40]
Fischbach, M.A.; Walsh, C.T. Antibiotics for emerging pathogens. Science, 2009, 325(5944), 1089-1093.
[http://dx.doi.org/10.1126/science.1176667] [PMID: 19713519]
[41]
Li, X.Z.; 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]
[42]
Lomovskaya, O.; Lewis, K. Emr, an Escherichia coli locus for multidrug resistance. Proc. Natl. Acad. Sci. USA, 1992, 89(19), 8938-8942.
[http://dx.doi.org/10.1073/pnas.89.19.8938] [PMID: 1409590]
[43]
Robinson, A.; Thomas, G.L.; Spandl, R.J.; Welch, M.; Spring, D.R. Gemmacin B: bringing diversity back into focus. Org. Biomol. Chem., 2008, 6(16), 2978-2981.
[http://dx.doi.org/10.1039/b809038f] [PMID: 18688491]
[44]
Wyatt, E.E.; Galloway, W.R.J.D.; Thomas, G.L.; Welch, M.; Loiseleur, O.; Plowright, A.T.; Spring, D.R. Identification of an anti-MRSA dihydrofolate reductase inhibitor from a diversity-oriented synthesis. Chem. Commun. Camb., 2008, 40(40), 4962-4964.
[http://dx.doi.org/10.1039/b812901k] [PMID: 18931753]
[45]
Von Döhren, H. Antibiotics: Actions, origins, resistance, by C. Walsh. 2003. Washington, DC: ASM Press. 345 pp. $99.95 (hardcover). Protein Sci., 2004, 13(11), 3059-3060.
[http://dx.doi.org/10.1110/ps.041032204]
[46]
Romero-Calle, D.; Guimarães Benevides, R.; Góes-Neto, A.; Billington, C. Bacteriophages as alternatives to antibiotics in clinical care. Antibiotics (Basel), 2019, 8(3), 138.
[http://dx.doi.org/10.3390/antibiotics8030138] [PMID: 31487893]
[47]
Perera, M.N.; Abuladze, T.; Li, M.; Woolston, J.; Sulakvelidze, A. Bacteriophage cocktail significantly reduces or eliminates Listeria monocytogenes contamination on lettuce, apples, cheese, smoked salmon and frozen foods. Food Microbiol., 2015, 52, 42-48.
[http://dx.doi.org/10.1016/j.fm.2015.06.006] [PMID: 26338115]
[48]
World Health Organization. Antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline, including tuberculosis; World Health Organization: Geneva, 2017, pp. 11-45.
[49]
Blair, J.M.; Webber, M.A.; Baylay, A.J.; Ogbolu, D.O.; Piddock, L.J. Molecular mechanisms of antibiotic resistance. Nat. Rev. Microbiol., 2015, 13(1), 42-51.
[http://dx.doi.org/10.1038/nrmicro3380] [PMID: 25435309]

Rights & Permissions Print Cite
Article Metrics
7
© 2024 Bentham Science Publishers | Privacy Policy