Correlation of overexpression of efflux pump genes with antibiotic resistance in Escherichia coli Strains clinically isolated from urinary tract infection patients.
Escherichia coli is one of the most common pathogens in urinary tract infections (UTIs), and antibiotic resistance in E. coli is becoming a serious problem in treating UTI. Efflux system overexpression is reported to contribute to E. coli resistance to several antibiotics. This study investigated the correlation of antibiotic susceptibilities with the overexpression of the efflux pump genes such as marA, yhiU, yhiV, and mdfA and with risk factors for antibiotic resistance in E. coli isolated from UTI patients. We examined the expression level of efflux pump genes using quantitative real-time reverse transcription-PCR (qRT-PCR). We also tested the in vitro susceptibilities to 12 kinds of antibiotics in 64 clinical strains of E. coli isolated from UTI patients. By multivariate analyses we revealed significant relationships between the overexpression of (i) marA and MICs of cefepime (FEP) and nalidixic acid (NAL), (ii) yhiV and MICs of minocycline (MIN), and (iii) mdfA and MICs of sitafloxacin (STX). In our investigation of the efflux pump genes, risk factors such as gender and the previous use of fluoroquinolones correlated with the overexpression of marA, and indwelling catheter use correlated with the overexpression of mdfA. In conclusion, we demonstrated that the increased expression of efflux pump genes such as marA and mdfA can lead to fluoroquinolone resistance in E. coli. These results contribute to our knowledge of the efflux system and raise the possibility of developing new agents, such as efflux pump inhibitors (EPIs), to antibiotic-resistant E. coli.
Department of Surgery, Division of Urology, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
Tomihiko
T
Yasufuku
Katsumi
K
Shigemura
Toshiro
T
Shirakawa
Minori
M
Matsumoto
Yuzo
Y
Nakano
Kazushi
K
Tanaka
Soichi
S
Arakawa
Shouhiro
S
Kinoshita
Masato
M
Kawabata
Masato
M
Fujisawa
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000378:metabolism*; 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 / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005796:Genes; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014552:Urinary Tract Infections / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger