Correlation Between Virulence Genotype and Fluoroquinolone Resistance in Carbapenem-Resistant Pseudomonas aeruginosa

Abstract

BackgroundPseudomonas aeruginosa is a clinically important pathogen that causes opportunistic 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 target site mutations in 66 carbapenem-resistant P. aeruginosa strains.MethodsSixty-six carbapenem-resistant P. aeruginosa strains were collected from patients in a university hospital in Daejeon, Korea, from January 2008 to May 2012. Minimum inhibitory concentrations (MICs) of fluoroquinolones (ciprofloxacin and levofloxacin) were determined by using the agar dilution method. We used PCR and sequencing to determine the TTSS effector genotype and quinolone resistance-determining regions (QRDRs) of the respective target genes gyrA, gyrB, parC, and parE.ResultsA 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.ConclusionsThe 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.

Molecular Detection of the VirulentExoUGenotype ofPseudomonas aeruginosaIsolated from Infected Surgical Incisions

“…Consistent with the current finding regarding the high prevalence of fluoroquinolone resistance in ExoU isolates (100%), Wong-Beringer et al [38] found that 92% of ExoU were fluoroquinolone-resistant compared with 61% resistance in ExoS. The association between MDR and the presence of the ExoU genotype has been associated with poor clinical outcome in patients with pneumonia in two different studies, particularly in immunocomporomised patients [39,40], with no clear genetic explanation. Proper surveillance for the emergence of the cytotoxic and MDR P. aeruginosa isolates would be essential for preventing serious P. aeruginosa outbreaks in surgical wards.…”

Detection of Exotoxins and Antimicrobial Susceptibility Pattern in Clinical Pseudomonas Aeruginosa Isolates

“…In this study, all of the isolates showed at least one of the exotoxin and the prevalence of exoU (5). These findings are contrary to our results.…”

“…The type III secretion system (TTSS) has been known to be a major virulence, which is determined in pathogenesis of acute infection, bacteremia, sepsis and subsequent mortality. The TTSS allows the injection of toxins into the cytosol of target eukaryotic cells, where they destroy host cell defense and signaling systems and that subsequently rapid call necrosis or modulating the actin cytoskeleton (4)(5)(6). Four effector proteins have been identified: ExoU, which is a phospholipase and it has been characterized as a major virulence factor in acute lung injury, ExoY that is an adenylate cyclase, and ExoS and ExoT which are bifunctional proteins (5,6).…”

“…Four effector proteins have been identified: ExoU, which is a phospholipase and it has been characterized as a major virulence factor in acute lung injury, ExoY that is an adenylate cyclase, and ExoS and ExoT which are bifunctional proteins (5,6). ExoU and ExoS are present variably and in pathogenesis are important, whereas the almost of isolates, ExoT and ExoY encode and have a minor effect on virulence (4,5). Previous studies have shown that production of ExoU was correlated with increasing virulence (7).…”

“…The TTSS allows the injection of toxins into the cytosol of target eukaryotic cells, where they destroy host cell defense and signaling systems and that subsequently rapid call necrosis or modulating the actin cytoskeleton (4)(5)(6). Four effector proteins have been identified: ExoU, which is a phospholipase and it has been characterized as a major virulence factor in acute lung injury, ExoY that is an adenylate cyclase, and ExoS and ExoT which are bifunctional proteins (5,6). ExoU and ExoS are present variably and in pathogenesis are important, whereas the almost of isolates, ExoT and ExoY encode and have a minor effect on virulence (4,5).…”