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Anti-Infective Agents

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ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

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Research Article

Polyaminosteroid Analogues as Potent Antibacterial Agents Against Mupirocin- Resistant Staphylococcus aureus Strains

Author(s): Adèle Sakr, Fréderic Laurent, Jean-Michel Brunel, Tania Nawfal Dagher, Olivier Blin and Jean-Marc Rolain *

Volume 18, Issue 3, 2020

Page: [239 - 244] Pages: 6

DOI: 10.2174/2211352517666190723092347

Abstract

Background: Nasal carriage of Staphylococcus aureus (S. aureus) constitutes an important risk factor for subsequent infections in some types of patient populations. Decolonization of carriers using intranasal mupirocin is widely used as a preventive measure. However, resistance to this agent has been rising and causing failure in the decolonization, highlighting the need for new alternatives.

Objective: The objective of our study was to evaluate the antibacterial activity of polyaminosteroid analogues (squalamine and BSQ-1) against S. aureus strains with different levels of mupirocin-resistance.

Methods: Using the broth microdilution method, we evaluated the minimum inhibitory concentration (MIC) of these molecules against S. aureus clinical strains including mupirocin-resistant strains. The emergence of resistance was evaluated by long-term and repeated exposure of a susceptible S. aureus strain to subinhibitory concentrations of squalamine, BSQ-1 or mupirocin.

Results: We found that squalamine and BSQ-1 are active against mupirocin-susceptible and -resistant clinical isolates with MIC values of 3.125 μg/mL. Additionally, repeated exposure of a S. aureus strain to squalamine and BSQ-1 did not lead to the emergence of resistant bacteria, contrarily to mupirocin.

Conclusion: Our study suggests that these molecules constitute promising new alternatives to mupirocin for nasal decolonization and prevention of endogenous infections.

Keywords: Polyaminosteroid analogues, squalamine analogues, Staphylococcus aureus, mupirocin-resistant S. aureus, mupirocin, nasal decolonization.

Graphical Abstract

[1]
von Eiff, C.; Becker, K.; Machka, K.; Stammer, H.; Peters, G. Study Group. Nasal carriage as a source of Staphylococcus aureus bacteremia. N. Engl. J. Med., 2001, 344(1), 11-16.
[http://dx.doi.org/10.1056/NEJM200101043440102] [PMID: 11136954]
[2]
Kalmeijer, M.D.; van Nieuwland-Bollen, E.; Bogaers-Hofman, D.; de Baere, G.A.; Jan Kluytmans, A.J.W. Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopedic surgery. Infect. Control Hosp. Epidemiol., 2000, 21(5), 319-323.
[http://dx.doi.org/10.1086/501763] [PMID: 10823564]
[3]
Kluytmans, J.A.; Mouton, J.W.; Ijzerman, E.P.; Vandenbroucke-Grauls, C.M.; Maat, A.W.; Wagenvoort, J.H.; Verbrugh, H.A. Nasal carriage of Staphylococcus aureus as a major risk factor for wound infections after cardiac surgery. J. Infect. Dis., 1995, 171(1), 216-219.
[http://dx.doi.org/10.1093/infdis/171.1.216] [PMID: 7798667]
[4]
Luzar, M.A.; Coles, G.A.; Faller, B.; Slingeneyer, A.; Dah, G.D.; Briat, C.; Wone, C.; Knefati, Y.; Kessler, M.; Peluso, F. Staphylococcus aureus nasal carriage and infection in patients on continuous ambulatory peritoneal dialysis. N. Engl. J. Med., 1990, 322(8), 505-509.
[http://dx.doi.org/10.1056/NEJM199002223220804] [PMID: 2300122]
[5]
Nardi, G.; Di Silvestre, A.D.; De Monte, A.; Massarutti, D.; Proietti, A.; Grazia Troncon, M.; Lesa, L.; Zussino, M. Reduction in gram-positive pneumonia and antibiotic consumption following the use of a SDD protocol including nasal and oral mupirocin. Eur. J. Emerg. Med., 2001, 8(3), 203-214.
[http://dx.doi.org/10.1097/00063110-200109000-00008] [PMID: 11587466]
[6]
Bode, L.G.; Kluytmans, J.A.; Wertheim, H.F.; Bogaers, D.; Vandenbroucke-Grauls, C.M.; Roosendaal, R.; Troelstra, A.; Box, A.T.; Voss, A.; van der Tweel, I.; van Belkum, A.; Verbrugh, H.A.; Vos, M.C. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N. Engl. J. Med., 2010, 362(1), 9-17.
[http://dx.doi.org/10.1056/NEJMoa0808939] [PMID: 20054045]
[7]
Schweizer, M.L.; Chiang, H-Y.; Septimus, E.; Moody, J.; Braun, B.; Hafner, J.; Ward, M.A.; Hickok, J.; Perencevich, E.N.; Diekema, D.J.; Richards, C.L.; Cavanaugh, J.E.; Perlin, J.B.; Herwaldt, L.A. Association of a bundled intervention with surgical site infections among patients undergoing cardiac, hip, or knee surgery. JAMA, 2015, 313(21), 2162-2171.
[http://dx.doi.org/10.1001/jama.2015.5387] [PMID: 26034956]
[8]
Tacconelli, E.; Carmeli, Y.; Aizer, A.; Ferreira, G.; Foreman, M.G.; D’Agata, E.M. Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients undergoing dialysis: a meta-analysis. Clin. Infect. Dis., 2003, 37(12), 1629-1638.
[http://dx.doi.org/10.1086/379715] [PMID: 14689344]
[9]
Lee, A.S.; Macedo-Vinas, M.; François, P.; Renzi, G.; Schrenzel, J.; Vernaz, N.; Pittet, D.; Harbarth, S. Impact of combined low-level mupirocin and genotypic chlorhexidine resistance on persistent methicillin-resistant Staphylococcus aureus carriage after decolonization therapy: a case-control study. Clin. Infect. Dis., 2011, 52(12), 1422-1430.
[http://dx.doi.org/10.1093/cid/cir233] [PMID: 21628482]
[10]
Poovelikunnel, T.; Gethin, G.; Humphreys, H. Mupirocin resistance: clinical implications and potential alternatives for the eradication of MRSA. J. Antimicrob. Chemother., 2015, 70(10), 2681-2692.
[http://dx.doi.org/10.1093/jac/dkv169] [PMID: 26142407]
[11]
Walker, E.S.; Vasquez, J.E.; Dula, R.; Bullock, H.; Sarubbi, F.A. Mupirocin-resistant, methicillin-resistant Staphylococcus aureus: does mupirocin remain effective? Infect. Control Hosp. Epidemiol., 2003, 24(5), 342-346.
[http://dx.doi.org/10.1086/502218] [PMID: 12785407]
[12]
Moore, K.S.; Wehrli, S.; Roder, H.; Rogers, M.; Forrest, J.N., Jr; McCrimmon, D.; Zasloff, M. Squalamine: an aminosterol antibiotic from the shark. Proc. Natl. Acad. Sci. USA, 1993, 90(4), 1354-1358.
[http://dx.doi.org/10.1073/pnas.90.4.1354] [PMID: 8433993]
[13]
Alhanout, K.; Rolain, J.M.; Brunel, J.M. Squalamine as an example of a new potent antimicrobial agents class: a critical review. Curr. Med. Chem., 2010, 17(32), 3909-3917.
[http://dx.doi.org/10.2174/092986710793205417] [PMID: 20858213]
[14]
Zasloff, M.; Adams, A.P.; Beckerman, B.; Campbell, A.; Han, Z.; Luijten, E.; Meza, I.; Julander, J.; Mishra, A.; Qu, W.; Taylor, J.M.; Weaver, S.C.; Wong, G.C. Squalamine as a broad-spectrum systemic antiviral agent with therapeutic potential. Proc. Natl. Acad. Sci. USA, 2011, 108(38), 15978-15983.
[http://dx.doi.org/10.1073/pnas.1108558108] [PMID: 21930925]
[15]
Bhargava, P.; Marshall, J.L.; Dahut, W.; Rizvi, N.; Trocky, N.; Williams, J.I.; Hait, H.; Song, S.; Holroyd, K.J.; Hawkins, M.J. A phase I and pharmacokinetic study of squalamine, a novel antiangiogenic agent, in patients with advanced cancers. Clin. Cancer Res., 2001, 7(12), 3912-3919.
[PMID: 11751482]
[16]
Djouhri-Bouktab, L.; Vidal, N.; Rolain, J.M.; Brunel, J.M. Synthesis of new 3,20-bispolyaminosteroid squalamine analogues and evaluation of their antimicrobial activities. J. Med. Chem., 2011, 54(20), 7417-7421.
[http://dx.doi.org/10.1021/jm200506x] [PMID: 21905738]
[17]
Loncle, C.; Salmi, C.; Letourneux, Y.; Brunel, J.M. Synthesis of new 7-aminosterol squalamine analogues with high antimicrobial activities through a stereoselective titanium reductive amination reaction. Tetrahedron, 2007, 63(52), 12968-12974.
[http://dx.doi.org/10.1016/j.tet.2007.10.032]
[18]
Alhanout, K.; Malesinki, S.; Vidal, N.; Peyrot, V.; Rolain, J.M.; Brunel, J.M. New insights into the antibacterial mechanism of action of squalamine. J. Antimicrob. Chemother., 2010, 65(8), 1688-1693.
[http://dx.doi.org/10.1093/jac/dkq213] [PMID: 20551217]
[19]
Trouillet-Assant, S.; Flammier, S.; Sapin, A.; Dupieux, C.; Dumitrescu, O.; Tristan, A.; Vandenesch, F.; Rasigade, J.P.; Laurent, F. Mupirocin Resistance in Isolates of Staphylococcus spp. from Nasal Swabs in a Tertiary Hospital in France. J. Clin. Microbiol., 2015, 53(8), 2713-2715.
[http://dx.doi.org/10.1128/JCM.00274-15] [PMID: 26019208]
[20]
O’Shea, S.; Cotter, L.; Creagh, S.; Lydon, S.; Lucey, B. Mupirocin resistance among staphylococci: trends in the southern region of Ireland. J. Antimicrob. Chemother., 2009, 64(3), 649-650.
[http://dx.doi.org/10.1093/jac/dkp227] [PMID: 19567406]
[21]
Staphylococcus aureus subsp. aureus Rosenbach (ATCC® 25923™) (Avaiable from https://www.lgcstandards-atcc.org/Pro-ducts/All/25923.aspx?geo_country=fr
[22]
Rolain, J.M.; François, P.; Hernandez, D.; Bittar, F.; Richet, H.; Fournous, G.; Mattenberger, Y.; Bosdure, E.; Stremler, N.; Dubus, J.C.; Sarles, J.; Reynaud-Gaubert, M.; Boniface, S.; Schrenzel, J.; Raoult, D. Genomic analysis of an emerging multiresistant Staphylococcus aureus strain rapidly spreading in cystic fibrosis patients revealed the presence of an antibiotic inducible bacteriophage. Biol. Direct, 2009, 4, 1.
[http://dx.doi.org/10.1186/1745-6150-4-1] [PMID: 19144117]
[23]
Jones, S.R.; Selinsky, B.S.; Rao, M.N.; Zhang, X.; Kinney, W.A.; Tham, F.S. Efficient Route to 7α-(Benzoyloxy)-3-dioxolane Cholestan-24(R)-ol, a Key Intermediate in the Synthesis of Squalamine. J. Org. Chem., 1998, 63(11), 3786-3789.
[http://dx.doi.org/10.1021/jo971405d]
[24]
Rao, M.N.; McGuigan, M.A.; Zhang, X.; Shaked, Z.; Kinney, W.A.; Bulliard, M.; Laboue, B.; Lee, N.E. Practical Approaches to Remote Asymmetric Induction in Steroidal Side-Chains Utilizing Oxazaborolidine Reagents. J. Org. Chem., 1997, 62(13), 4541-4545.
[http://dx.doi.org/10.1021/jo970227l] [PMID: 11671794]
[25]
Zhang, X.; Rao, M.N.; Jones, S.R.; Shao, B.; Feibush, P.; McGuigan, M.; Tzodikov, N.; Feibush, B.; Sharkansky, I.; Snyder, B.; Mallis, L.M.; Sarkahian, A.; Wilder, S.; Turse, J.E.; Kinney, W.A.; Kjærsgaard, H.J. Michalak, R.S. Synthesis of Squalamine Utilizing a Readily Accessible Spermidine Equivalent. J. Org. Chem., 1998, 63(23), 8599-8603.
[http://dx.doi.org/10.1021/jo981344z]
[26]
Cockerill, F.R.; Wikler, M.A.; Alder, J.; Dudley, M.N.; Eliopoulos, G.M.; Ferraro, M.J.; Hardy, D.J.; Hecht, D.W.; Hindler, J.A.; Patel, J.B.; Powell, M.; Swenson, J.M.; Thomson, R.B.; Traczewski, M.M.; Turnbrighe, J.D.; Weinstein, M.P.; Zimmer, B.L. Methods for Dilution An-timicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Ninth Edition; , 2012, 18, p. 32.
[27]
Lee, A.S.; Gizard, Y.; Empel, J.; Bonetti, E.J.; Harbarth, S.; François, P. Mupirocin-induced mutations in ileS in various genetic backgrounds of methicillin-resistant Staphylococcus aureus. J. Clin. Microbiol., 2014, 52(10), 3749-3754.
[http://dx.doi.org/10.1128/JCM.01010-14] [PMID: 25122856]
[28]
Septimus, E.J.; Schweizer, M.L. Decolonization in Prevention of Health Care-Associated Infections. Clin. Microbiol. Rev., 2016, 29(2), 201-222.
[http://dx.doi.org/10.1128/CMR.00049-15] [PMID: 26817630]
[29]
Ward, A.; Campoli-Richards, D.M. Mupirocin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs, 1986, 32(5), 425-444.
[http://dx.doi.org/10.2165/00003495-198632050-00002] [PMID: 3098541]
[30]
Perl, T.M.; Cullen, J.J.; Wenzel, R.P.; Zimmerman, M.B.; Pfaller, M.A.; Sheppard, D.; Twombley, J.; French, P.P.; Herwaldt, L.A. Mupirocin And The Risk Of Staphylococcus Aureus Study Team. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N. Engl. J. Med., 2002, 346(24), 1871-1877.
[http://dx.doi.org/10.1056/NEJMoa003069] [PMID: 12063371]
[31]
De Jonge, S.; Atema, J.J.; Gans, S.; Boermeester, M.A.; Gomes, S.M.; Solomkin, J.S.; Van Rijen, M.; Kluytmans, J.; Allegranzi, B.; Bis-choff, P.; De Jonge, S.; Kubilay, Z.; Zayed, B.; Gomes, S.M.; Abbas, M.; Atema, J.J.; Gans, S.; Van Rijen, M.; Boermeester, M.A.; Egger, M.; Kluytmans, J.; Pittet, D.; Solomkin, J.S. Surgical site infections 1 New WHO recommendations on preoperative measures for surgical site infection prevention: an evidence-based global perspective. Lancet Infect. Dis., 2016, 16(12)
[http://dx.doi.org/10. 1016/S1473-3099(16)30398-X]
[32]
Gurney, R.; Thomas, C.M. Mupirocin: biosynthesis, special features and applications of an antibiotic from a gram-negative bacterium. Appl. Microbiol. Biotechnol., 2011, 90(1), 11-21.
[http://dx.doi.org/10.1007/s00253-011-3128-3] [PMID: 21336932]
[33]
Monecke, S.; Ruppelt-Lorz, A.; Müller, E.; Reissig, A.; Thürmer, A.; Shore, A.C.; Coleman, D.C.; Ehricht, R.; Jatzwauk, L. Dissemination of high-level mupirocin-resistant CC22-MRSA-IV in Saxony. GMS Hyg. Infect. Control, 2017, 12, Doc19.
[PMID: 29184755]
[34]
Rudresh, M.S.; Ravi, G.S.; Motagi, A.; Alex, A.M.; Sandhya, P.; Navaneeth, B.V. Prevalence of Mupirocin Resistance Among Staphylococci, its Clinical Significance and Relationship to Clinical Use. J. Lab. Physicians, 2015, 7(2), 103-107.
[http://dx.doi.org/10.4103/0974-2727.163127] [PMID: 26417160]
[35]
Seah, C.; Alexander, D.C.; Louie, L.; Simor, A.; Low, D.E.; Longtin, J.; Melano, R.G. MupB, a new high-level mupirocin resistance mechanism in Staphylococcus aureus. Antimicrob. Agents Chemother., 2012, 56(4), 1916-1920.
[http://dx.doi.org/10.1128/AAC.05325-11] [PMID: 22252810]
[36]
Simor, A.E.; Phillips, E.; McGeer, A.; Konvalinka, A.; Loeb, M.; Devlin, H.R.; Kiss, A. Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization. Clin. Infect. Dis., 2007, 44(2), 178-185.
[http://dx.doi.org/10.1086/510392] [PMID: 17173213]
[37]
Rotger, M.; Trampuz, A.; Piper, K.E.; Steckelberg, J.M.; Patel, R. Phenotypic and genotypic mupirocin resistance among Staphylococci causing prosthetic joint infection. J. Clin. Microbiol., 2005, 43(8), 4266-4268.
[http://dx.doi.org/10.1128/JCM.43.8.4266-4268.2005] [PMID: 16081996]
[38]
Pobiega, M.; Myjak, I.; Pomorska-Wesolowska, M.; Romaniszyn, D.; Ziolkowski, G.; Chmielarczyk, A.; Macig, J.; Szczypta, A.; Wójkowska-Mach, J. Virulence potential of staphylococcus aureus strains isolated from diabetic foot ulcers among patients from southern poland. Curr. Vasc. Pharmacol., 2016, 14(6), 547-551.
[http://dx.doi.org/10.2174/1570161114666160625083742] [PMID: 27357184]
[39]
Blanchet, M.; Borselli, D.; Rodallec, A.; Peiretti, F.; Vidal, N.; Bolla, J.M.; Digiorgio, C.; Morrison, K.R.; Wuest, W.M.; Brunel, J.M. Claramines: A New Class Of Broad-Spectrum Antimicrobial Agents With Bimodal Activity. ChemMedChem, 2018, 13(10), 1018-1027.
[http://dx.doi.org/10.1002/cmdc.201800073] [PMID: 29465814]

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