نقش ژن mexZ در مقاومت به سیپروفلوکساسین در جدایه های سودوموناس آئروژینوزا در استان گیلان

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Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas aeruginosa.Int J Antimicrob Agents 2003;21(5):409-13. Morita Y, Sobel ML, Poole K. Antibiotic inducibility of the MexXY multidrug efflux system of Pseudomonas aeruginosa: involvement of the antibiotic-inducible PA5471 gene product. J Bacteriol 2006;188(5):1847-55. Aires JR, Kohler T, Nikaido H, Plesiat P. Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides. Antimicrob Agents Chemother 1999;43(11):2624-8. Morita Y, Tomida J, Kawamura Y. MexXY multidrug efflux system of Pseudomonas aeruginosa. Front Microbiol 2012;3:408. Poole K. Outer membranes and efflux: the path to multidrug resistance in Gram-negative bacteria. Curr Pharm Biotechnol 2002;3(2):77-98. Masuda N, Sakagawa E, Ohya S, Gotoh N, Tsujimoto H, Nishino T. Contribution of the MexX-MexY-oprM efflux system to intrinsic resistance in Pseudomonas aeruginosa. 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The pattern of antibiotic resistance and Metallo-β-lactamases production in pseudomonas aeruginosa isolated  from  Clinical samples of  Dr Ganjavian Hospital in Dezful. J Microbial Biotechnol 2012;4(14):21-8. Kalantar E, Taherzadeh S, Ghadimi T, Soheili F, Salimizand H, Hedayatnejad A. Pseudomonas aeruginosa, an emerging pathogen among burn patients in Kurdistan Province, Iran. Southeast Asian J Trop Med Public Health 2012;43(3):712-7. Negi N, Prakash P, Gupta ML, Mohapatra TM. Possible Role of Curcumin as an Efflux Pump Inhibitor in Multi Drug Resistant Clinical Isolates of Pseudomonas aeruginosa. J Clin Diagn Res 2014;8(10):DC04-7. Yamamoto M, Ueda A, Kudo M, Matsuo Y, Fukushima J, Nakae T, et al. Role of MexZ and PA5471 in transcriptional regulation of mexXY in Pseudomonas aeruginosa. Microbiol 2009;155(Pt 10):3312-21. Hocquet D, Berthelot P, Roussel-Delvallez M, Favre R, Jeannot K, Bajolet O, et al. Pseudomonas aeruginosa may accumulate drug resistance mechanisms without losing its ability to cause bloodstream infections. Antimicrob Agents Chemother 2007;51(10):3531-6. Geyik MF, Aldemir M, Hosoglu S, Tacyildiz HI. Epidemiology of burn unit infections in children. Am J Infection Control 2003;31(6):342-6. Llanes C, Hocquet D, Vogne C, Benali-Baitich D, Neuwirth C, Plesiat P. Clinical strains of Pseudomonas aeruginosa overproducing MexAB-OprM and MexXY efflux pumps simultaneously. Antimicrob Agents Chemother 2004;48(5):1797-802.   Background & Aims: Pseudomonas aeruginosa is an opportunistic pathogen and one of mortality causes of nosocomial infections specifically in severely burned patients. One of the drug resistant mechanisms in pseudomonas aeruginosa is mutation in negative regulator genes of mexXY efflux pump system. In this study, the role of mexZ mutations was investigated in ciprofloxacin resistant development in Pseudomonas aeruginosa isolates in Guilan province. Materials & Methods: In this study, 45 strains of pseudomonas aeruginosa isolated from different clinical samples of Rasht and Lahijan hospitals and laboratories between 2014 to 2016 were identified by biochemical tests. The antibiotic resistance and susceptibility of the strains were investigated by Kirby Bauer method and MIC determination. Then PCR-sequencing was performed to assess MexZ gene mutations in ciprofloxacin resistant strains. Results: From 45 isolates of pseudomonas aeruginosa, all were resistant to cefixime, cephalothin and trimethoprim; whereas 17 isolates were ciprofloxacin resistant. The highest MIC of ciprofloxacin was determined 1024 µg/ml. Also, PCR-sequencing analysis showed that 8 isolates had missense mutations in MexZ gene such as L111E and R143P. Conclusion: In this study, mutation in mexZ as negative regulator of mexXY can be a reason of multi-drug resistance in some strains in Guilan province. It appears that mexZ mutation led to affinity modification in mexZ protein binding to DNA in some isolates. SOURCE: URMIA MED J 2016: 26(10): 913 ISSN: 1027-3727