Hasdemir Ufuk Over, Chevalier Jacqueline, Nordmann Patrice, Pagès Jean-Marie
Department of Microbiology, School of Medicine, Marmara University, Istanbul, Turkey.
J Clin Microbiol. 2004 Jun;42(6):2701-6. doi: 10.1128/JCM.42.6.2701-2706.2004.
The prevalence of active drug efflux pump and porin alterations was investigated in Turkish nosocomial strains of Klebsiella pneumoniae exhibiting a multidrug-resistant phenotype. MICs of various antibiotics, including quinolones, chloramphenicol, tetracycline, and beta-lactams, for those strains were determined either with or without the efflux pump inhibitor phenylalanine arginine beta-naphthylamide (PAbetaN). Thirty-nine percent of the strains exhibited a PAbetaN-modulated resistance for quinolones, chloramphenicol, and tetracycline. In these strains, a significant increase of chloramphenicol accumulation was gained in the presence of the efflux pump inhibitor PAbetaN or with the energy uncoupler carbonyl cyanide m-chlorophenylhydrazone. Moreover, high-level expression of the membrane fusion protein AcrA, which was immunodetected in most of those isolates, suggests that the AcrAB/TolC efflux machinery contributed to their antibiotic resistance. Studies of K. pneumoniae porins indicated that the majority of the strains, including extended-spectrum beta-lactamase producers and efflux-positive ones, presented an alteration in their sorbitol-sensitive porin (OmpK35) expression. This is the first report showing the prominent role of active drug efflux in the antibiotic resistance of nosocomial K. pneumoniae strains from Turkey.
在土耳其表现出多重耐药表型的医院分离肺炎克雷伯菌菌株中,研究了活性药物外排泵和孔蛋白改变的发生率。使用或不使用外排泵抑制剂苯丙氨酸精氨酸β-萘酰胺(PAbetaN),测定了这些菌株对包括喹诺酮类、氯霉素、四环素和β-内酰胺类在内的各种抗生素的最低抑菌浓度(MIC)。39%的菌株对喹诺酮类、氯霉素和四环素表现出PAbetaN调节的耐药性。在这些菌株中,在存在外排泵抑制剂PAbetaN或能量解偶联剂羰基氰化物间氯苯腙的情况下,氯霉素积累显著增加。此外,在大多数这些分离株中通过免疫检测到的膜融合蛋白AcrA的高水平表达表明,AcrAB/TolC外排机制导致了它们的抗生素耐药性。肺炎克雷伯菌孔蛋白的研究表明,大多数菌株,包括产超广谱β-内酰胺酶的菌株和外排阳性菌株,其山梨醇敏感孔蛋白(OmpK35)表达发生改变。这是第一份显示活性药物外排在来自土耳其的医院肺炎克雷伯菌菌株抗生素耐药性中起重要作用的报告。