title: Correlation between virulence genotype and fluoroquinolone resistance in carbapenem-resistant Pseudomonas aeruginosa.
abstract: 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.
authors: Department of Biomedical Laboratory Science, Jeonju Kijeon College, Jeonju, Korea.
authors: Hye Hyun
authors: HH
authors: Cho
authors: Department of Laboratory Medicine, College of Medicine, Chungnam National University, Daejeon, Korea.
authors: Kye Chul
authors: KC
authors: Kwon
authors: Department of Laboratory Medicine, College of Medicine, Chungnam National University, Daejeon, Korea.
authors: Semi
authors: S
authors: Kim
authors: Department of Laboratory Medicine, College of Medicine, Chungnam National University, Daejeon, Korea.
authors: Sun Hoe
authors: SH
authors: Koo
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics; D015780:Carbapenems / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D024841:Fluoroquinolones / Q000494:pharmacology*; D005838:Genotype; D006801:Humans; D008826:Microbial Sensitivity Tests; D058885:Multilocus Sequence Typing; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D013183:Sputum / Q000382:microbiology; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015780:Carbapenems; D024841:Fluoroquinolones; C111749:pseudomonas exoprotein A protein, Pseudomonas aeruginosa; D036002:ADP Ribose Transferases; C444820:exoenzyme S
keywords: Fluoroquinolone resistance; TTSS effector genotype; exoS; exoU