Does mutation in gyrA and/or parC or efflux pump expression play the main role in fluoroquinolone resistance in Escherichia coli urinary tract infections?: A statistical analysis study.
There are several mechanisms of fluoroquinolone (FQ) resistance, such as mutations in the quinolone resistance-determining regions (QRDRs) of target genes and efflux pump expression. The purpose of this study was to investigate which factor plays the main role in FQ resistance in Escherichia coli causing urinary tract infections (UTIs) from a statistical analysis of our two previous works. DNA sequencing of the QRDRs of the FQ resistance-related genes gyrA and parC as well as real-time reverse transcriptase (RT)-PCR for the expression of efflux pump genes such as marA or yhiU were performed and the correlations of mutations or efflux pump gene expression with FQ minimal inhibitory concentrations (MICs) were investigated. Significant factors for high MICs of sitafloxacin (STFX), ciprofloxacin (CPFX) and levofloxacin were the mutations S83L and D87N in gyrA and S80I and E84V in parC as well as the expression of marA. Mutations in the QRDRs of gyrA or parC had a greater effect on FQ MICs than efflux pump gene expression. Based on the regression coefficient, these mutations correlated with MICs to CPFX most, and STFX had the lowest effects from these mutations among the three tested FQs. In conclusion, in E. coli causing UTIs, mutations in the QRDRs of gyrA or parC had a greater effect on FQ resistance, especially to CPFX, than efflux pump gene expression from a statistical analysis study of our two previous works. Further research into the molecular basis for FQ resistance could lead to new therapeutic strategies against FQ-resistant E. coli.
Department of Surgery, Division of Urology, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. yutoshunta@hotmail.co.jp
Katsumi
K
Shigemura
Kazushi
K
Tanaka
Fukashi
F
Yamamichi
Toshiro
T
Shirakawa
Hideaki
H
Miyake
Masato
M
Fujisawa
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D004927:Escherichia coli Infections / Q000382:microbiology*; D029968:Escherichia coli Proteins / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014552:Urinary Tract Infections / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D024841:Fluoroquinolones; D026901:Membrane Transport Proteins; D050505:Mutant Proteins; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase