MexXY efflux pump overexpression and aminoglycoside resistance in cystic fibrosis isolates of pseudomonas aeruginosa from chronic infections

Canadian Journal of Microbiology

Volumn 63, Issue 12, 2017, Pages 929-938

  Singh, Manu ^a   Yau, Yvonne C W ^b   Wang, Shirley ^a   Waters, Valerie ^b   Kumar, Ayush ^a,b  

^a UNIVERSITY OF MANITOBA   (Canada)

^b HOSPITAL FOR SICK CHILDREN   (Canada)

Author keywords

Aminoglycoside resistance; MexZ; Regulatory gene mutations

Indexed keywords

AMINOGLYCOSIDE; NUCLEOTIDE; RNA DIRECTED DNA POLYMERASE; ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; MEXXY PROTEIN, PSEUDOMONAS AERUGINOSA;

ANTIBIOTIC RESISTANCE; BACTERIAL DISEASE; BACTERIUM; GENE EXPRESSION; MUTATION;

ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL SECRETION SYSTEM; BACTERIUM ISOLATE; CYSTIC FIBROSIS; GENE MUTATION; GENE SEQUENCE; LUNG INFECTION; MICROBIAL ACTIVITY; NONHUMAN; OPERON; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; PSEUDOMONAS AERUGINOSA; REGULATOR GENE; RESISTANCE NODULATION DIVISION PUMP; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; ANTIBIOTIC RESISTANCE; COMPLICATION; DRUG EFFECTS; GENE EXPRESSION; GENETICS; MICROBIOLOGY; MULTIDRUG RESISTANCE; MUTATION; PSEUDOMONAS INFECTION;

PSEUDOMONAS AERUGINOSA;

AMINOGLYCOSIDES; ANTI-BACTERIAL AGENTS; BACTERIAL PROTEINS; CYSTIC FIBROSIS; DRUG RESISTANCE, BACTERIAL; DRUG RESISTANCE, MULTIPLE; GENE EXPRESSION; MUTATION; PSEUDOMONAS AERUGINOSA; PSEUDOMONAS INFECTIONS;

EID: 85034586069     PISSN: 00084166     EISSN: 14803275     Source Type: Journal    
DOI: 10.1139/cjm-2017-0380     Document Type: Article

References (51)

1. Aires, J.R., Köhler, T., Nikaido, H., and Plésiat, P. 1999. Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob. Agents Chemother. 43(11): 2624-2628. PMID:10543738.
2. Alguel, Y., Lu, D., Quade, N., Sauter, S., and Zhang, X. 2010. Crystal structure of MexZ, a key repressor responsible for antibiotic resistance in Pseudomonas aeruginosa. J. Struct. Biol. 172(3): 305-310. doi:10.1016/j.jsb.2010.07.012. PMID:20691272.
3. Alvarez-Ortega, C., Olivares, J., and Martínez, J.L. 2013. RND multidrug efflux pumps: What are they good for? Front. Microbiol. 4: 7. doi:10.3389/fmicb.2013.00007. PMID:23386844.
4. Cystic Fibrosis Canada. 2015. The Canadian Cystic Fibrosis Registry 2013 annual report. Cystic Fibrosis Canada, Toronto, Ont., Canada. Available from http://www.cysticfibrosis.ca/uploads/cf%20 care/Canadian-CF-Registry-2013-FINAL.pdf.
5. CLSI (Clinical and Laboratory Standards Institute). 2006. M100-S16: performance standards for antimicrobial susceptibility testing. Sixteeth informational supplement. Clinical and Laboratory Standards Institute, Wayne, Pa., USA.
6. CLSI (Clinical and Laboratory Standards Institute). 2017. M100-27: performance standards for antimicrobial susceptibility testing. 27th ed. Clinical and Laboratory Standards Institute, Wayne, Pa., USA.
7. Eaves, D.J., Ricci, V., and Piddock, L.J. 2004. Expression of acrB, acrF, acrD, marA, and soxS in Salmonella enterica serovar Typhimurium: role in multiple antibiotic resistance. Antimicrob. Agents Chemother. 48(4): 1145-1150. doi:10.1128/AAC.48.4. 1145-1150.2004. PMID:15047514.
8. Fernando, D., and Kumar, A. 2012. Growth phase-dependent expression of RND efflux pump-and outer membrane porinencoding genes in Acinetobacter baumannii ATCC 19606. J. Antimicrob. Chemother. 67(3): 569-572. doi:10.1093/jac/dkr519. PMID:22146875.
9. Fernando, D., Zhanel, G., and Kumar, A. 2013. Antibiotic resistance and expression of resistance-nodulation-division pumps and outer membrane porins in Acinetobacter species isolated from Canadian hospitals. Can. J. Infect. Dis. Med. Microbiol. 24(1): 17-21. PMID:24421787.
10. Guénard, S., Muller, C., Monlezun, L., Benas, P., Broutin, I., Jeannot, K., and Plésiat, P. 2014. Multiple mutations lead to MexXY-OprM-dependent aminoglycoside resistance in clinical strains of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 58(1): 221-228. doi:10.1128/AAC.01252-13. PMID: 24145539.
11. Henrichfreise, B., Wiegand, I., Pfister, W., and Wiedemann, B. 2007. Resistance mechanisms of multiresistant Pseudomonas aeruginosa strains from Germany and correlation with hypermutation. Antimicrob. Agents Chemother. 51(11): 4062-4070. doi:10.1128/AAC.00148-07. PMID:17876002.
12. Hocquet, D., Roussel-Delvallez, M., Cavallo, J.-D., and Plésiat, P. 2007. MexAB-OprM-and MexXY-overproducing mutants are very prevalent among clinical strains of Pseudomonas aeruginosa with reduced susceptibility to ticarcillin. Antimicrob. Agents Chemother. 51(4): 1582-1583. doi:10.1128/AAC. 01334-06. PMID:17220417.
13. Jeannot, K., Sobel, M.L., El Garch, F., Poole, K., and Plésiat, P. 2005. Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drug-ribosome interaction. J. Bacteriol. 187(15): 5341-5346. doi:10.1128/JB.187.15.5341-5346.2005. PMID:16030228.
14. Jeannot, K., Elsen, S., Köhler, T., Attree, I., van Delden, C., and Plésiat, P. 2008. Resistance and virulence of Pseudomonas aeruginosa clinical strains overproducing the MexCD-OprJ efflux pump. Antimicrob. Agents Chemother. 52(7): 2455-2462. doi:10.1128/AAC.01107-07. PMID:18474583.
15. Jones, R.N., Holliday, N.M., and Krause, K.M. 2015. Validation of sensititre dry-form broth microdilution panels for susceptibility testing of ceftazidime-avibactam, a broad-spectrum-_-lactamase inhibitorcombination. Antimicrob.AgentsChemother. 59(8): 5036-5039. doi:10.1128/AAC.00021-15. PMID:26014937.
16. Köhler, T., Michéa-Hamzehpour, M., Henze, U., Gotoh, N., Curty, L.K., and Pechère, J.-C. 1997. Characterization of MexEMexF-OprN, a positively regulated multidrug efflux system of Pseudomonas aeruginosa. Mol. Microbiol. 23: 345-354. doi:10. 1046/j.1365-2958.1997.2281594.x. PMID:9044268.
17. Korting, H.C., Neubert, U., and Abeck, D. 1998. Current antimicrobial susceptibility of cutaneous bacteria to first line antibiotics. Int. J. Antimicrob. Agents, 10(2): 165-168. doi:10.1016/S0924-8579(98)00023-5. PMID:9716294.
18. Kumar, A., and Schweizer, H.P. 2005. Bacterial resistance to antibiotics: active efflux and reduced uptake. Adv. Drug Delivery Rev. 57(10): 1486-1513. doi:10.1016/j.addr.2005.04.004.
19. Kumar, A., and Schweizer, H.P. 2011. Evidence of MexTindependent overexpression of MexEF-OprN multidrug efflux pump of Pseudomonas aeruginosa in presence of metabolic stress. PLoS One, 6(10): e26520. doi:10.1371/journal.pone. 0026520. PMID:22039504.
20. Kumar, A., Mayo, M., Trunck, L.A., Cheng, A.C., Currie, B.J., and Schweizer, H.P. 2008. Expression of resistance-nodulationcell-division efflux pumps in commonly used Burkholderia pseudomallei strains and clinical isolates from northern Aus-tralia. Trans. R. Soc. Trop. Med. Hyg. 102: S145-S151. doi:10. 1016/S0035-9203(08)70032-4. PMID:19121677.
21. Li, X.-Z., Nikaido, H., and Poole, K. 1995. Role of mexA-mexB-oprM in antibiotic efflux in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 39(9): 1948-1953. doi:10.1128/AAC.39.9. 1948. PMID:8540696.
22. Li, X.-Z., Plésiat, P., and Nikaido, H. 2015. The challenge of effluxmediated antibiotic resistance in Gram-negative bacteria. Clin. Microbiol. Rev. 28(2): 337-418. doi:10.1128/CMR.00117-14. PMID:25788514.
23. Llanes, C., Hocquet, D., Vogne, C., Benali-Baitich, D., Neuwirth, C., and Plésiat, P. 2004. Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob. Agents Chemother. 48(5): 1797-1802. doi:10.1128/AAC.48.5.1797-1802.2004. PMID:15105137.
24. Maseda, H., Saito, K., Nakajima, A., and Nakae, T. 2000. Variation of the mexT gene, a regulator of the MexEF-OprN efflux pump expression in wild-type strains of Pseudomonas aeruginosa. FEMS Microbiol. Lett. 192: 107-112. doi:10.1111/j. 1574-6968.2000.tb09367.x. PMID:11040437.
25. Masuda, N., Sakagawa, E., Ohya, S., Gotoh, N., Tsujimoto, H., and Nishino, T. 2000a. Contribution of the MexX-MexYOprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 44: 2242-2246. doi:10.1128/AAC.44.9.2242-2246.2000. PMID:10952562.
26. Masuda, N., Sakagawa, E., Ohya, S., Gotoh, N., Tsujimoto, H., and Nishino, T. 2000b. Substrate specificities of MexABOprM, MexCD-OprJ, and MexXY-OprM efflux pumps in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 44: 3322-3327. doi:10.1128/AAC.44.12.3322-3327.2000. PMID: 11083635.
27. Mesaros, N., Nordmann, P., Plésiat, P., Roussel-Delvallez, M., Van Eldere, J., Glupczynski, Y., et al. 2007. Pseudomonas aeruginosa: resistance and therapeutic options at the turn of the new millennium. Clin. Microbiol. Infect. 13(6): 560-578. doi: 10.1111/j.1469-0691.2007.01681.x. PMID:17266725.
28. Mine, T., Morita, Y., Kataoka, A., Mizushima, T., and Tsuchiya, T. 1999. Expression in Escherichia coli of a new multidrug efflux pump, MexXY, from Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 43(2): 415-417. PMID:9925549.
29. Morita, Y., Sobel, M.L., and Poole, K. 2006. Antibiotic inducibility of the MexXY multidrug efflux system of Pseudomonas aeruginosa: involvement of the antibiotic-inducible PA5471 gene product. J. Bacteriol. 188(5): 1847-1855. doi:10.1128/JB. 188.5.1847-1855.2006. PMID:16484195.
30. Morita, Y., Gilmour, C., Metcalf, D., and Poole, K. 2009. Translational control of the antibiotic inducibility of the PA5471 gene required for mexXY multidrug efflux gene expression in Pseudomonas aeruginosa. J. Bacteriol. 191(15): 4966-4975. doi:10.1128/JB.00073-09. PMID:19465646.
31. Muller, C., Plésiat, P., and Jeannot, K. 2011. A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and _-lactams in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 55(3): 1211-1221. doi: 10.1128/AAC.01252-10. PMID:21149619.
32. Nikaido, H., and Takatsuka, Y. 2009. Mechanisms of RND multidrug efflux pumps. Biochim. Biophys. Acta, Proteins Proteomics, 1794(5): 769-781. doi:10.1016/j.bbapap.2008.10.004. PMID:19026770.
33. Pfaffl, M.W. 2001. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29(9): e45. doi:10.1093/nar/29.9.e45. PMID:11328886.
34. Poole, K. 2012. Bacterial stress responses as determinants of antimicrobial resistance. J. Antimicrob. Chemother. 67(9): 2069-2089. doi:10.1093/jac/dks196. PMID:22618862.
35. Poole, K., Krebes, K., McNally, C., and Neshat, S. 1993. Multiple antibiotic resistance in Pseudomonas aeruginosa: evidence for involvement of an efflux operon. J. Bacteriol. 175(22): 7363-7372. doi:10.1128/jb.175.22.7363-7372.1993. PMID:8226684.
36. Poonsuk, K., Tribuddharat, C., and Chuanchuen, R. 2014. Simultaneous overexpression of multidrug efflux pumps in Pseudomonas aeruginosa non-cystic fibrosis clinical isolates. Can. J. Microbiol. 60(7): 437-443. doi:10.1139/cjm-2014-0239. PMID:24909060.
37. Purssell, A., and Poole, K. 2013. Functional characterization of the NfxB repressor of the mexCD-oprJ multidrug efflux operon of Pseudomonas aeruginosa. Microbiology, 159: 2058-2073. doi: 10.1099/mic.0.069286-0. PMID:23924707.
38. Quale, J., Bratu, S., Gupta, J., and Landman, D. 2006. Interplay of efflux system, ampC, and oprD expression in carbapenem resistance of Pseudomonas aeruginosa clinical isolates. Antimicrob. Agents Chemother. 50(5): 1633-1641. doi:10.1128/AAC. 50.5.1633-1641.2006. PMID:16641429.
39. Ratjen, F., Brockhaus, F., and Angyalosi, G. 2009. Aminoglycoside therapy against Pseudomonas aeruginosa in cystic fibrosis: a review. J. Cystic Fibrosis, 8(6): 361-369. doi:10.1016/j.jcf.2009. 08.004.
40. Richardot, C., Juarez, P., Jeannot, K., Patry, I., Plésiat, P., and Llanes, C. 2016. Amino acid substitutions account for most MexS alterations in clinical nfxC mutants of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 60(4): 2302-2310. doi:10.1128/AAC.02622-15. PMID:26833155.
41. Smith, E.E., Buckley, D.G., Wu, Z., Saenphimmachak, C., Hoffman, L.R., D’Argenio, D.A., et al. 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. U.S.A. 103(22): 8487-8492. doi: 10.1073/pnas.0602138103. PMID:16687478.
42. Sobel, M.L., Neshat, S., and Poole, K. 2005. Mutations in PA2491 (mexS) promote MexT-dependent mexEF-oprN expression and multidrug resistance in a clinical strain of Pseudomonas aeruginosa. J. Bacteriol. 187(4): 1246-1253. doi:10.1128/JB.187.4. 1246-1253.2005. PMID:15687188.
43. Solé, M., Fabrega, A., Cobos-Trigueros, N., Zamorano, L., Ferrer-Navarro, M., Ballesté-Delpierre, C., et al. 2015. In vivo evolution of resistance of Pseudomonas aeruginosa strains isolated from patients admitted to an intensive care unit: mechanisms of resistance and antimicrobial exposure. J. Antimicrob. Chemother. 70(11): 3004-3013. doi:10.1093/jac/dkv228. PMID:26260130.
44. Uwate, M., Ichise, Y.K., Shirai, A., Omasa, T., Nakae, T., and Maseda, H. 2013. Two routes of MexS-MexT-mediated regulation of MexEF-OprN and MexAB-OprM efflux pump expression in Pseudomonas aeruginosa. Microbiol. Immunol. 57(4): 263-272. doi:10.1111/1348-0421.12032. PMID:23586630.
45. Vettoretti, L., Plésiat, P., Muller, C., El Garch, F., Phan, G., Attrée, I., et al. 2009. Efflux unbalance in Pseudomonas aeruginosa isolates from cystic fibrosis patients. Antimicrob. Agents Chemother. 53(5): 1987-1997. doi:10.1128/AAC.01024-08. PMID: 19258280.
46. Weinstein, R.A., Gaynes, R., and Edwards, J.R. 2005. Overview of nosocomial infections caused by Gram-negative bacilli. Clin. Infect. Dis. 41(6): 848-854. doi:10.1086/432803. PMID:16107985.
47. Wolter, D.J., Black, J.A., Lister, P.D., and Hanson, N.D. 2009. Multiple genotypic changes in hypersusceptible strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients do not always correlate with the phenotype. J. Antimicrob. Chemother. 64(2): 294-300. doi:10.1093/jac/dkp185. PMID: 19468029.
48. Yau, Y.C.W., Ratjen, F., Tullis, E., Wilcox, P., Freitag, A., Chilvers, M., et al. 2015. Randomized controlled trial of biofilm antimicrobial susceptibility testing in cystic fibrosis patients. J. Cystic Fibrosis, 14(2): 262-266. doi:10.1016/j.jcf.2014. 09.013.
49. Young, D.C., Zobell, J.T., Stockmann, C., Waters, C.D., Ampofo, K., Sherwin, C.M., and Spigarelli, M.G. 2013. Op-timization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: V. Aminoglycosides. Pediatr. Pulmonol. 48(11): 1047-1061. doi:10.1002/ppul.22813. PMID:24000183.
50. Zhanel, G.G., DeCorby, M., Laing, N., Weshnoweski, B., Vashisht, R., Tailor, F., et al. 2008. Antimicrobial-resistant pathogens in intensive care units in Canada: results of the Canadian National Intensive Care Unit (CAN-ICU) study, 2005-2006. Antimicrob. Agents Chemother. 52(4): 1430-1437. doi:10.1128/AAC.01538-07. PMID:18285482.
51. Zhanel, G.G., DeCorby, M., Adam, H., Mulvey, M.R., McCracken, M., Lagacé-Wiens, P., et al. 2010. Prevalence of antimicrobial-resistant pathogens in Canadian hospitals: results of the Canadian Ward surveillance study (CANWARD 2008). Antimicrob. Agents Chemother. 54(11): 4684-4693. doi: 10.1128/AAC.00469-10. PMID:20805395.