Correlation Between Virulence Genotype and Fluoroquinolone Resistance in Carbapenem-Resistant Pseudomonas aeruginosa
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Pseudomonas aeruginosa is a clinically important pathogen that causes op- portunistic infections and nosocomial outbreaks. Recently, the type III secretion system (TTSS) has been shown to play an important role in the virulence of P. aeruginosa . ExoU, in particular, has the greatest impact on disease severity. We examined the relationship among the TTSS effector genotype ( exoS and exoU ), fluoroquinolone resistance, and tar- get site mutations in 66 carbapenem-resistant P. aeruginosa strains. Methods: Sixty-six carbapenem-resistant P. aeruginosa strains were collected from pa- tients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Mini- mum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to de- termine the TTSS effector genotype and quinolone resistance-determining regions (QR- DRs) of the respective target genes gyrA, gyrB, parC , and parE . Results: A higher proportion of exoU+ strains were fluoroquinolone-resistant than exoS+ strains (93.2%, 41/44 vs. 45.0%, 9/20; P ≤0.0001). Additionally, exoU + strains were more likely to carry combined mutations than exoS + strains (97.6%, 40/41 vs. 70%, 7/10; P =0.021), and MIC increased as the number of active mutations increased. Conclusions: The recent overuse of fluoroquinolone has led to both increased resistance and enhanced virulence of carbapenem-resistant P. aeruginosa . These data indicate a specific relationship among exoU genotype, fluoroquinolone resistance, and resistance- conferring mutations.
Abstract
Background: Pseudomonas aeruginosa is a clinically important pathogen that causes op- portunistic infections and nosocomial outbreaks. Recently, the type III secretion system (TTSS) has been shown to play an important role in the virulence of P. aeruginosa . ExoU, in particular, has the greatest impact on disease severity. We examined the relationship among the TTSS effector genotype ( exoS and exoU ), fluoroquinolone resistance, and tar- get site mutations in 66 carbapenem-resistant P. aeruginosa strains. Methods: Sixty-six carbapenem-resistant P. aeruginosa strains were collected from pa- tients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Mini- mum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to de- termine the TTSS effector genotype and quinolone resistance-determining regions (QR- DRs) of the respective target genes gyrA, gyrB, parC , and parE . Results: A higher proportion of exoU+ strains were fluoroquinolone-resistant than exoS+ strains (93.2%, 41/44 vs. 45.0%, 9/20; P ≤0.0001). Additionally, exoU + strains were more likely to carry combined mutations than exoS + strains (97.6%, 40/41 vs. 70%, 7/10; P =0.021), and MIC increased as the number of active mutations increased. Conclusions: The recent overuse of fluoroquinolone has led to both increased resistance and enhanced virulence of carbapenem-resistant P. aeruginosa . These data indicate a specific relationship among exoU genotype, fluoroquinolone resistance, and resistance- conferring mutations.
참고문헌 (40)
- Shaver CM, "Relative contributions of Pseudomonas aeruginosa ExoU, ExoS, and ExoT to virulence in the lung", Infect Immun, 72, pp.6969~6977 (2004)
- Galán JE, "Type III secretion machines: bacterial devices for protein delivery into host cells", Science, 284, pp.1322~1328 (1999)
- Wong-Beringer A, "Comparison of type III secretion system virulence among fluoroquinolone-susceptible and -resistant clinical isolates of Pseudomonas aeruginosa", Clin Microbiol Infect, 14, pp.330~336 (2008)
- Veesenmeyer JL, "Pseudomonas aeruginosa virulence and therapy: evolving translational strategies", Crit Care Med, 37, pp.1777~1786 (2009)
- Frank DW, "The exoenzyme S regulon of Pseudomonas aeruginosa", Mol Microbiol, 26, pp.621~629 (1997)
- Sato H, "ExoU is a potent intracellular phospholipase", Mol Microbiol, 53, pp.1279~1290 (2004)
- Feltman H, "Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa", Microbiology, 147, pp.2659~2669 (2001)
- Fleiszig SM, "Pseudomonas aeruginosa-mediated cytotoxicity and invasion correlate with distinct genotypes at the loci encoding exoenzyme S", Infect Immun, 65, pp.579~586 (1997)
- Roy-Burman A, "Type III protein secretion is associated with death in lower respiratory and systemic Pseudomonas aeruginosa infections", J Infect Dis, 183, pp.1767~1774 (2001)
- Schulert GS, "Secretion of the toxin ExoU is a marker for highly virulent Pseudomonas aeruginosa isolates obtained from patients with hospital-acquired pneumonia", J Infect Dis, 188, pp.1695~1706 (2003)
- El Solh AA, "Persistent infection with Pseudomonas aeruginosa in ventilator-associated pneumonia", Am J Respir Crit Care Med, 178, pp.513~519 (2008)
- Thomson CJ, "The global epidemiology of resistance to ciprofloxacin and the changing nature of antibiotic resistance: a 10 year perspective", J Antimicrob Chemother, 43(SA), pp.31~40 (1999)
- Karlowsky JA, "Surveillance for antimicrobial susceptibility among clinical isolates of Pseudomonas aeruginosa and Acinetobacter baumannii from hospitalized patients in the United States, 1998 to 2001", Antimicrob Agents Chemother, 47, pp.1681~1688 (2003)
- 이경원, "Korean Nationwide Surveillance of Antimicrobial Resistance in 2000 with Special Reference to Vancomycin Resistance in Enterococci, and Expanded- Spectrum Cephalosporin and Imipenem Resistance", Yonsei Medical Journal, 44(4), pp.571~578 (2003), 연세대학교의과대학
- Lee Kyungwon, "Increasing Prevalence of Vancomycin-Resistant Enterococcus faecium, Expanded-Spectrum Cephalosporin-Resistant Klebsiella pneumoniae, and Imipenem-Resistant Pseudomonas aeruginosa in Korea", Journal of Korean Medical Science, 19(1), pp.8~14 (2004), 대한의학회
- Ko KS, "OprD mutations and inactivation, expression of efflux pumps and AmpC, and metallo-beta-lactamases in carbapenem-resistant Pseudomonas aeruginosa isolates from South Korea", INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 40, pp.168~172 (2012), ELSEVIER SCIENCE BV
- Ruiz J, "Mechanisms of resistance to quinolones: target alterations, decreased accumulation and DNA gyrase protection", J Antimicrob Chemother, 51, pp.1109~1117 (2003)
- Valdezate S, "Topoisomerase II and IV quinolone resistance-determining regions in Stenotrophomonas maltophilia clinical isolates with different levels of quinolone susceptibility", Antimicrob Agents Chemother, 46, pp.665~671 (2002)
- Mouneimné H, "Type II topoisomerase mutations in ciprofloxacin-resistant strains of Pseudomonas aeruginosa", Antimicrob Agents Chemother, 43, pp.62~66 (1999)
- Vila J, "Quinolone-resistance mutations in the topoisomerase IV parC gene of Acinetobacter baumannii", J Antimicrob Chemother, 39, pp.757~762 (1997)
- Sáenz Y, "Mutations in gyrA and parC genes in nalidixic acid-resistant Escherichia coli strains from food products, humans and animals", J Antimicrob Chemother, 51, pp.1001~1005 (2003)
- Clinical and Laboratory Standards Institute, "Performance standards for antimicrobial susceptibility testing: Twentieth Informational supplement, M100-S20", Clinical and Laboratory Standards Institute, ~ (2010)
- Agnello M, "Differentiation in quinolone resistance by virulence genotype in Pseudomonas aeruginosa", PLoS One, 7, pp.42973~ (2012)
- Lee JK, "Alterations in the GyrA and GyrB Subunits of topoisomerase II and the ParC and ParE subunits of topoisomerase IV in ciprofloxacin-resistant clinical isolates of Pseudomonas aeruginosa", INT J ANTIMICROBIAL AGENTS, 25, pp.290~295 (2005)
- Gasink LB, "Fluoroquinolone-resistant Pseudomonas aeruginosa: assessment of risk factors and clinical impact", Am J Med, 119(526), pp.19~25 (2006)
- Jalal S, "Molecular mechanisms of fluoroquinolone resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients", Antimicrob Agents Chemother, 44, pp.710~712 (2000)
- Holder IA, "Type III secretion", intoxication system important in virulence of Pseudomonas aeruginosa infections in burns, 2001, pp.27, 129~130
- Kulasekara BR, "Acquisition and evolution of the exoU locus in Pseudomonas aeruginosa", J Bacteriol, 188, pp.4037~4050 (2006)
- Hauser AR, "Type III protein secretion is associated with poor clinical outcomes in patients with ventilator-associated pneumonia caused by Pseudomonas aeruginosa", Crit Care Med, 30, pp.521~528 (2002)
- Hsu DI, "Fluoroquinolone-resistant Pseudomonas aeruginosa: risk factors for acquisition and impact on outcomes", J Antimicrob Chemother, 55, pp.535~541 (2005)
- Kwon KC, "Prevalence and Genetic Analysis of Multidrug-Resistant Pseudomonas aeruginosa ST235 Isolated from a Hospital in Korea, 2008-2012", ANNALS OF CLINICAL AND LABORATORY SCIENCE, 43(4), pp.414~419 (2013), ASSOC CLINICAL SCIENTISTS
- Peck KR, "Selective advantages of two major clones of carbapenem-resistant Pseudomonas aeruginosa isolates (CC235 and CC641) from Korea: antimicrobial resistance, virulence and biofilm-forming activity", JOURNAL OF MEDICAL MICROBIOLOGY, 62, pp.1015~1024 (2013), SOC GENERAL MICROBIOLOGY
- Matsumoto M, "Mutations in the gyrA and parC genes and in vitro activities of fluoroquinolones in 114 clinical isolates of Pseudomonas aeruginosa derived from urinary tract infections and their rapid detection by denaturing high-performance liquid chromatography", Int J Antimicrob Agents, 40, pp.440~444 (2012)
- Hrabák J, "Regional spread of Pseudomonas aeruginosa ST357 producing IMP-7 metallo-β-lactamase in Central Europe", J Clin Microbiol, 49, pp.474~475 (2011)
- Nakano M, "Mutations in the gyrA and parC genes in fluoroquinolone-resistant clinical isolates of Pseudomonas aeruginosa", Antimicrob Agents Chemother, 41, pp.2289~2291 (1997)
- Higgins PG, "Mutations in GyrA, ParC, MexR and NfxB in clinical isolates of Pseudomonas", Int J Antimicrob Agents, 21, pp.409~413 (2003)
- Akasaka T, "Type II topoisomerase mutations in fluoroquinolone-resistant clinical strains of Pseudomonas aeruginosa isolated in 1998 and 1999: role of target enzyme in mechanism of fluoroquinolone resistance", Antimicrob Agents Chemother, 45, pp.2263~2268 (2001)
- Oh H, "Role of efflux pumps and mutations in genes for topoisomerase II and IV in fluoroquiniolone-resistant Pseudomonas aeruginosa strains", Microb Drug Resist, 9, pp.323~328 (2003)
- Shultz TR, "Correlation of in vitro susceptibilities to newer quinolones of naturally occurring quinolone-resistant Neisseria gonorrhoeae strains with changes in GyrA and ParC", Antimicrob Agents Chemother, 45, pp.734~738 (2001)
- Parry CM, "Suitable disk antimicrobial susceptibility breakpoints defining Salmonella enterica serovar Typhi isolates with reduced susceptibility to fluoroquinolones", Antimicrob Agents Chemother, 54, pp.5201~5208 (2010)