Relationship between the expression of ompF and quinolone resistance in Escherichia coli.
The outer membrane porin protein, OmpF, is widely found in gram-negative bacteria. It is known that the decreased expression of OmpF causes resistance to multiple antibiotics, including quinolones. In order to characterize the influence of decreased OmpF expression on bacterial growth, the fitness of the ompF and gyrA mutant strain of Escherichia coli selected experimentally with quinolone was compared with that of the parent strain. The expression levels of ompF in clinical isolates and the mutant selected with quinolone were determined by real-time PCR. The bacterial growth of the experimentally selected mutants was also measured both in vitro and in a urinary tract infection model in mice. Decreased ompF phenotypes were frequently found in clinical isolates that exhibited alteration of topoisomerases. The mutant experimentally obtained by the resistance selection process with quinolone showed no loss of fitness either in vitro or in vivo. These results suggest that the decreased expression of ompF and gyrA mutation do not affect the survival of the bacteria, and in fact may be responsible for the spread of high-level resistance to quinolones.
Kishii
Ryuta
R
Exploratory Research Laboratories, Kyorin Pharmaceutical Co. Ltd., 2399-1 Nogi, Nogi-machi, Shimotsuga, Tochigi, 329-0114, Japan. ryuuta.kishii@mb.kyorin-pharm.co.jp
Takei
Masaya
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D048708:Cell Growth Processes / Q000187:drug effects; D002939:Ciprofloxacin / Q000494:pharmacology*; D027081:DNA Gyrase / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000382:microbiology; D015870:Gene Expression; D005816:Genetic Complementation Test; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D009154:Mutation; D009643:Norfloxacin / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D018272:Porins / Q000096:biosynthesis* / Q000235:genetics
D000900:Anti-Bacterial Agents; C109237:OmpF protein; D018272:Porins; D002939:Ciprofloxacin; D027081:DNA Gyrase; D009643:Norfloxacin