Correlation between virulence genotype and fluoroquinolone resistance in carbapenem-resistant Pseudomonas aeruginosa
Hye Hyun Cho1, Kye Chul Kwon2, Semi Kim2
1Department of Biomedical Laboratory Science, Jeonju Kijeon College, Jeonju, Korea.
Background:
Pseudomonas 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.
Methods:
Sixty-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.
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.
Insights
Carbapenem-resistant Pseudomonas aeruginosa strains with the exoU gene showed higher fluoroquinolone resistance and more mutations than those with the exoS gene. This highlights a link between specific virulence factors and antibiotic resistance.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Pseudomonas aeruginosa is a significant opportunistic pathogen causing hospital-acquired infections.
- The type III secretion system (TTSS) is crucial for P. aeruginosa virulence, with ExoU being a key effector impacting disease severity.
- Carbapenem resistance in P. aeruginosa is a growing clinical concern.
Purpose of the Study:
- To investigate the relationship between TTSS effector genotype (exoS vs. exoU) and fluoroquinolone resistance in carbapenem-resistant P. aeruginosa.
- To analyze the correlation between TTSS genotype, fluoroquinolone resistance, and target site mutations.
Main Methods:
- Sixty-six carbapenem-resistant P. aeruginosa strains were analyzed.
- Fluoroquinolone (ciprofloxacin, levofloxacin) minimum inhibitory concentrations (MICs) were determined.
- PCR and sequencing were used to identify TTSS effector genotypes and mutations in quinolone resistance-determining regions (gyrA, gyrB, parC, parE).
Main Results:
- Strains with the exoU genotype exhibited significantly higher fluoroquinolone resistance (93.2%) compared to exoS strains (45.0%).
- exoU+ strains were more likely to possess multiple resistance mutations (97.6%) than exoS+ strains (70%).
- Increasing numbers of resistance mutations correlated with higher MIC values.
Conclusions:
- Fluoroquinolone overuse contributes to increased resistance and virulence in carbapenem-resistant P. aeruginosa.
- A distinct association exists between the exoU genotype, heightened fluoroquinolone resistance, and the presence of specific resistance mutations.
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