Exploratory Research Laboratories, Kyorin Pharmaceutical Co. Ltd., 2399-1 Nogi, Nogi-machi, Shimotsuga, Tochigi, 329-0114, Japan.
J Infect Chemother. 2009 Dec;15(6):361-6. doi: 10.1007/s10156-009-0716-6.
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.
外膜孔蛋白 OmpF 在革兰氏阴性菌中广泛存在。已知 OmpF 表达减少会导致对多种抗生素(包括喹诺酮类)产生耐药性。为了研究 OmpF 表达减少对细菌生长的影响,我们比较了经喹诺酮类药物实验选择的 ompF 和 gyrA 突变株大肠杆菌的适应度与亲株的适应度。通过实时 PCR 确定了临床分离株和经喹诺酮类药物选择的突变株中 ompF 的表达水平。还在体外和小鼠尿路感染模型中测量了实验选择的突变体的细菌生长情况。在表现出拓扑异构酶改变的临床分离株中经常发现 ompF 表型减少。通过喹诺酮类药物耐药选择过程获得的突变体在体外和体内均未显示出适应性丧失。这些结果表明,ompF 表达减少和 gyrA 突变不会影响细菌的生存能力,实际上可能是导致高水平喹诺酮类耐药性传播的原因。