Multiple mutations lead to MexXY-OprM-dependent aminoglycoside resistance in clinical strains of pseudomonas aeruginosa

Antimicrobial Agents and Chemotherapy

Volumn 58, Issue 1, 2014, Pages 221-228

  Guénard, Sophie ^a   Muller, Cédric ^a   Monlezun, Laura ^b   Benas, Philippe ^b   Broutin, Isabelle ^b   Jeannot, Katy ^a   Plésiat, Patrick ^a  

^a UNIVERSITY HOSPITAL OF BESANÇON   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

Author keywords

[No Author keywords available]

Indexed keywords

AMIKACIN; AMINOGLYCOSIDE ANTIBIOTIC AGENT; AMPICILLIN; APRAMYCIN; BACTERIAL PROTEIN; CEFEPIME; CEFTAZIDIME; MEXXY PROTEIN; MEXZ PROTEIN; PROTEIN HISTIDINE KINASE; SIGNAL PEPTIDE; STREPTOMYCIN; TETRACYCLINE; TICARCILLIN; TOBRAMYCIN; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL GROWTH; CONTROLLED STUDY; DIMERIZATION; DNA BINDING; DNA SEQUENCE; GENE EXPRESSION; GENE MUTATION; GENE OVEREXPRESSION; GENE SEQUENCE; GENE STRUCTURE; GENOTYPE; NONHUMAN; OPERON; PRIORITY JOURNAL; PSEUDOMONAS AERUGINOSA; REPRESSOR GENE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS; UPREGULATION;

AMINOGLYCOSIDES; BACTERIAL PROTEINS; GENE EXPRESSION REGULATION, BACTERIAL; MICROBIAL SENSITIVITY TESTS; MUTATION; OPERON; PSEUDOMONAS AERUGINOSA;

EID: 84891524500     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.01252-13     Document Type: Article

References (54)

1. Lister PD, Wolter DJ, Hanson ND. 2009. Antibacterial-resistant Pseudomonas aeruginosa: Clinical impact and complex regulation of chromosomally encoded resistance mechanisms. Clin. Microbiol. Rev. 22:582- 610. http://dx.doi.org/10.1128/CMR.00040-09.
2. Aires JR, Köhler T, Nikaido H, Plésiat P. 1999. Involvement of an efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob. Agents Chemother. 43:2624-2628.
3. Dean CR, Visalli MA, Projan SJ, Sum P-E, Bradford PA. 2003. Effluxmediated resistance to tigecycline (GAR-936) in Pseudomonas aeruginosa PAO1. Antimicrob. Agents Chemother. 47:972-978. http://dx.doi.org/10.1128/AAC. 47.3.972-978.2003.
4. Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. 2000. Contribution of the MexX-MexY-OprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 44:2242-2246. http://dx.doi.org/10.1128/AAC.44.9.2242-2246.2000.
5. Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. 2000. Substrate specificities of MexAB-OprM, MexCD-OprJ, and MexXY-OprM efflux pumps in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 44:3322-3327. http://dx.doi.org/10.1128/AAC.44.12.3322-3327.2000.
6. Mine T, Morita Y, Kataoka A, Mizushima T, Tsuchiya T. 1999. Expression in Escherichia coli of a new multidrug efflux pump MexXY, from Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 43:415-417.
7. Westbrock-Wadman S, Sherman DR, Hickey MJ, Coulter SN, Zhu YQ, Warrener P, Nguyen LY, Shawar RM, Folger KR, Stover CK. 1999. Characterization of a Pseudomonas aeruginosa efflux pump contributing to aminoglycoside impermeability. Antimicrob. Agents Chemother. 43: 2975-2983.
8. Baum EZ, Crespo-Carbone SM, Morrow BJ, Davies TA, Foleno BD, He W, Queenan AM, Bush K. 2009. Effect of MexXY overexpression on ceftobiprole susceptibility in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53:2785-2790. http://dx.doi.org/10.1128/AAC.00018-09.
9. Hocquet D, Nordmann P, El Garch F, Cabanne L, Plésiat P. 2006. Involvement of the MexXY-OprM efflux system in emergence of cefepime resistance in clinical strains of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 50:1347-1351. http://dx.doi.org/10.1128/AAC.50.4.1347-1351.2006.
10. Jeannot K, Sobel ML, El Garch F, Poole K, Plésiat P. 2005. Induction of the MexXY efflux pump in Pseudomonas aeruginosa is dependent on drugribosome interaction. J. Bacteriol. 187:5341-5346. http://dx.doi.org/10. 1128/JB.187.15.5341-5346.2005.
11. Poole K, Heinrichs DE, Neshat S. 1993. Cloning and sequence analysis of an EnvCD homologue in Pseudomonas aeruginosa: regulation by iron and possible involvement in the secretion of the siderophore pyoverdine. Mol. Microbiol. 10:529-544.
12. Gotoh N, Tsujimoto H, Poole K, Yamagishi JI, Nishino T. 1995. The outer membrane protein OprM of Pseudomonas aeruginosa is encoded by oprK of the mexA-mexB-oprK multidrug resistance operon. Antimicrob. Agents Chemother. 39:2567-2569. http://dx.doi.org/10.1128/AAC.39.11.2567.
13. Morita Y, Sobel ML, Poole K. 2006. Antibiotic inducibility of the MexXY multidrug efflux system of Pseudomonas aeruginosa: Involvement of the antibiotic-inducible PA5471 gene product. J. Bacteriol. 188:1847-1855.http://dx. doi.org/10.1128/JB.188.5.1847-1855.2006.
14. Morita Y, Gilmour C, Metcalf D, 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: 4966-4975. http://dx.doi.org/10.1128/JB.00073-09.
15. Yamamoto M, Ueda A, Kudo M, Matsuo Y, Fukushima J, Nakae T, Kaneko T, Ishigatsubo Y. 2009. Role of MexZ and PA5471 in transcriptional regulation of mexXY in Pseudomonas aeruginosa. Microbiology 155: 3312-3321. http://dx.doi.org/10.1099/mic.0.028993-0.
16. Hay T, Fraud S, Lau CH-F, Gilmour C, Poole K. 2013. Antibiotic inducibility of the mexXY multidrug efflux operon of Pseudomonas aeruginosa: Involvement of the MexZ anti-repressor ArmZ. PLoS One 8(2):e56858. http://dx.doi.org/10.1371/journal.pone.0056858.
17. Matsuo Y, Eda S, Gotoh N, Yoshihara E, Nakae T. 2004. MexZmediated regulation of mexXY multidrug efflux pump expression in Pseudomonas aeruginosa by binding on the mexZ-mexX intergenic DNA. FEMS Microbiol. Lett. 238:23-28. http://dx.doi.org/10.1111/j.1574-6968.2004.tb09732.x.
18. Hocquet D, Muller A, Blanc K, Plésiat P, Talon D, Monnet DL, Bertrand X. 2008. Relationship between antibiotic use and incidence of MexXY-OprM overproducers among clinical isolates of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 52:1173-1175.
19. Vogne C, Ramos Aires J, Bailly C, Hocquet D, Plésiat P. 2004. Role of the multidrug efflux system MexXY in the emergence of moderate resistance to aminoglycosides among Pseudomonas aeruginosa isolates from patients with cystic fibrosis. Antimicrob. Agents Chemother. 48:1676-1680. http://dx.doi.org/10. 1128/AAC.48.5.1676-1680.2004.
20. Campo Esquisabel AB, Rodriguez MC, Campo-Sosa AO, Rodriguez C, Martinez-Martinez L. 2011. Mechanisms of resistance in clinical isolates of Pseudomonas aeruginosa less susceptible to cefepime than to ceftazidime. Clin. Microbiol. Infect. 17:1817-1822. http://dx.doi.org/10.1111/j.1469-0691.2011. 03530.x.
21. Sobel ML, McKay GA, Poole K. 2003. Contribution of the MexXY multidrug transporter to aminoglycoside resistance in Pseudomonas aeruginosa clinical isolates. Antimicrob. Agents Chemother. 47:3202-3207. http://dx.doi.org/10.1128/ AAC.47.10.3202-3207.2003.
22. Islam S, Jalal S, Wretling B. 2004. Expression of the MexXY efflux pump in amikacin-resistant isolates of Pseudomonas aeruginosa. Clin. Microbiol. Infect. 10:877-883. http://dx.doi.org/10.1111/j.1469-0691.2004.00991.x.
23. Llanes C, Hocquet D, Vogne C, Benali-Baitich D, Neuwirth C, Plésiat P. 2004. Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob. Agents Chemother. 48:1797-1802. http://dx.doi.org/10.1128/AAC.48.5.1797-1802.2004.
24. Muller C, Plésiat P, Jeannot K. 2011. A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and ß-lactams in Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 55:1211-1221. http://dx.doi.org/10.1128/AAC.01252-10.
25. Pasca MR, Dalla Valle C, De Jesus Lopes Ribeiro AL, Buroni S, Papaleo MC, Bazzini S, Udine C, Incandela ML, Daffara S, Fani R, Riccardi G, Marone P. 2012. Evaluation of fluoroquinolone resistance mechanisms in Pseudomonas aeruginosa multidrug resistance clinical isolates. Microb. Drug Resist. 18:23-32. http://dx.doi.org/10.1089/mdr.2011.0019.
26. Lau CH-F, Fraud S, Jones M, Peterson SN, Poole K. 2012. Reduced expression of the rplU-rpmA ribosomal protein operon in mexXY-expressing pan-aminoglycoside-resistant mutants of Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 56:5171-5179. http://dx.doi.org/10.1128/AAC.00846-12.
27. El'Garch F, Jeannot K, Hocquet D, Llanes-Barakat C, Plésiat P. 2007. Cumulative effects of several nonenzymatic mechanisms on the resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob. Agents Chemother. 51:1016-1021. http://dx.doi.org/10.1128/AAC.00704-06.
28. Caughlan RE, Sriram S, Daigle DM, Woods AL, Buco J, Peterson RL, Dzink- Fox J, Walker S, Dean CR. 2009. Fmt bypass in Pseudomonas aeruginosa causes induction of MexXY efflux pump expression. Antimicrob. Agents Chemother. 53:5015-5022. http://dx.doi.org/10.1128/AAC.00253-09.
29. Fournier D, Richardot C, Müller E, Robert-Nicoud M, Llanes C, Plésiat P, Jeannot K. 2013. Complexity of resistance mechanisms to imipenem in intensive care unit strains of Pseudomonas aeruginosa. J. Antimicrob. Chemother. 68:1772-1780. http://dx.doi.org/10.1093/jac/dkt098.
30. Ditta G, Stanfield S, Corbin D, Helinski DR. 1980. Broad host range DNA cloning system for gram-negative bacteria: Construction of a gene bank of Rhizobium meliloti. Proc. Natl. Acad. Sci. U. S. A. 77:7347-7351.
31. CLSI. 2006. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, 7th ed. CLSI, Wayne, PA.
32. Alguel Y, Lu D, Quade N, Sauter S, Zhang X. 2010. Crystal structure of MexZ, a key repressor responsible for antibiotic resistance in Pseudomonas aeruginosa. J. Struct. Biol. 172:305-310. http://dx.doi.org/10.1016/j.jsb.2010. 07.012.
33. Orth P, Schnappinger D, Hillen W, Saenger W, Hinrichs W. 2000. Structural basis of gene regulation by the tetracycline inducible Tet repressor-operator system. Nat. Struct. Biol. 7:215-219. http://dx.doi.org/10.1038/73324.
34. Emsley P, Cowtan K. 2004. Coot: Model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60:2126-2132. http://dx.doi.org/10.1107/S0907444904019158.
35. Waterhouse AM, Procter JB, Martin DM, Clamp M, Barton GJ. 2009. Jalview version 2: A multiple sequence alignment editor and analysis workbench. Bioinformatics 25:1189 -1191. http://dx.doi.org/10.1093/bioinformatics/btp033.
36. Hoang TT, Kutchma AJ, Becher A, Schweizer HP. 2000. Integrationproficient plasmids for Pseudomonas aeruginosa: Site-specific integration and use for engineering of reporter and expression strains. Plasmid 43:59-72. http://dx.doi.org/10.1006/plas.1999.1441.
37. Dumas J-L, vanDelden C, Perron K, Köhler T. 2006. Analysis of antibiotic resistance gene expression in Pseudomonas aeruginosa by quantitative real-time-PCR. FEMS Microbiol. Lett. 254:217-225. http://dx.doi.org/10.1111/j. 1574-6968.2005.00008.x.
38. Wiehlmann L, Wagner G, Cramer N, Siebert B, Gudowius P, Morales G, Köhler T, van Delden C, Weinel C, Slickers P, Tümmler B. 2007. Population structure of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. U. S. A. 19:8101-8106. http://dx.doi.org/10.1073/pnas.0609213104.
39. Cabot G, Ocampo-Sosa AA, Dominguez MA, Gago JF, Juan C, Tubau F, Rodriguez C, Moyà B, Pena C, Martinez-Martinez L, Oliver A, Spanish Network for Research in Infectious Diseases (REIPI). 2012. Genetic markers of widespread extensively drug-resistant Pseudomonas aeruginosa high-risk clones. Antimicrob. Agents Chemother. 56:6349-6357. http://dx.doi.org/10.1128/AAC.01388- 12.
40. Henrichfreise B, Wiegand I, Pfister W, Wiedemann B. 2007. Resistance mechanisms of multiresistant Pseudomonas aeruginosa strains from Germany and correlation with hypermutation. Antimicrob. Agents Chemother. 51:4062-4070. http://dx.doi.org/10.1128/AAC.00148-07.
41. Schumacher MA, Brennan RG. 2002. Structural mechanisms of multidrug recognition and regulation by bacterial multidrug transcription factors. Mol. Microbiol. 45:885-893. http://dx.doi.org/10.1046/j.1365-2698.2002.03039.x.
42. Le TBK, Schumacher MA, Lawson DM, Brennan RG, Buttner MJ. 2011. The crystal structure of the TetR family transcriptional repressor SimR bound to DNA and the role of a flexible N-terminal extension in minor groove binding. Nucleic Acids Res. 39:9433-9447. http://dx.doi.org/10.1093/nar/gkr640.
43. Morita Y, Tomida J, Kawamura Y. 2012. MexXY multidrug efflux system of Pseudomonas aeruginosa. Front. Microbiol. 3:408. http://dx.doi.org/10.3389./ fmicb.2012.00408.
44. Newton DT, Creuzenet C, Mangroo D. 1999. Formylation is not essential for initiation of protein synthesis in all eubacteria. J. Biol. Chem. 274: 22143-22146.
45. Williams SB, Stewart V. 1999. Functional similarities among twocomponent sensors and methyl-accepting chemotaxis proteins suggest a role for linker region amphipathic helices in transmembrane signal transduction. Mol. Microbiol. 33:1093-1102.
46. Qin X, Zerr DM, McNutt MA, Berry JE, Burns JL, Kapur RP. 2012. Pseudomonas aeruginosa synthrophy in chronically colonized airways of cystic fibrosis patients. Antimicrob. Agents Chemother. 56:5971-5981.http://dx.doi.org/ 10.1128/AAC.01371-12.
47. Mulcahy LR, Burns JL, Lory S, Lewis K. 2010. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J. Bacteriol. 192:6191-6199. http://dx.doi.org/10.1128/JB. 01651-09.
48. Feliziani S, Lujan AM, Moyano AJ, Sola C, Bocco JL, Montanaro P, Fernández Canigia L, Argaraña CE, Smania AM. 2010. Mucoidy, quorum sensing, mismatch repair and antibiotic resistance in Pseudomonas aeruginosa from cystic fibrosis chronic airways infections. PLoS One 5(9): e12669. http://dx.doi.org/10.1371/journal.pone.0012669.
49. Smith EE, Buckley DG, Wu Z, Saenphimmachak C, Hoffman LR, D'Argenio DA, Miller SI, Ramsey BW, Speert DP, Moskowitz SM, Burns JL, Kaul R, Olson MV. 2006. Genetic adaptation by Pseudomonas aeruginosa to the airways of cystic fibrosis patients. Proc. Natl. Acad. Sci. U. S. A. 103:8487-8492. http://dx.doi.org/10. 1073/pnas.0602138103.
50. Deplano A, Denis O, Poirel L, Hocquet D, Nonhoff C, Byl B, Nordmann P, Vincent JL, Struelens MJ. 2005. Molecular characterization of an epidemic clone of panantibiotic-resistant Pseudomonas aeruginosa. J. Clin. Microbiol. 43:1198-1204. http://dx.doi.org/10.1128/JCM.43.3.1198-1204.2005.
51. Llanes C, Köhler T, Patry I, Dehecq B, van Delden C, Plésiat P. 2011. Role of the MexEF-OprN efflux system in low-level resistance of Pseudomonas aeruginosa to ciprofloxacin. Antimicrob. Agents Chemother. 55: 5676-5684. http://dx.doi.org/10.1128/AAC.00101-11.
52. Hocquet D, Bertrand X, Köhler T, Talon D, Plésiat P. 2003. Genetic and phenotypic variations of a resistant Pseudomonas aeruginosa epidemic clone. Antimicrob. Agents Chemother. 47:1887-1894. http://dx.doi.org/10.1128/ AAC.47.6.1887-1894.2003.
53. Werckenthin C, Schwarz S, Westh H. 1999. Structural alterations in the translational attenuator of constitutively expressed ermC genes. Antimicrob. Agents Chemother. 43:1681-1685.
54. Manoil C, Beckwith J. 1985. TnphoA: A transposon probe for protein export signals. Proc. Natl. Acad. Sci. U. S. A. 82:8129-8133.