Villar H E, Danel F, Livermore D M
Department of Medical Microbiology, St Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
J Antimicrob Chemother. 1997 Sep;40(3):365-70. doi: 10.1093/jac/40.3.365.
An imipenem-resistant mutant of Proteus mirabilis lacked a 26 kDa outer membrane protein (OMP). It has previously been postulated that this protein is a porin, but the present mutant, which was cross-resistant to mecillinam but not to other beta-lactams, proved as permeable to carbapenems as its parent. A mecillinam-selected mutant had similar cross-resistance yet retained the 26 kDa OMP, confirming that this protein was not important to resistance. In contrast, cefoxitin-selected mutants retained the 26 kDa protein but had diminished expression of major 41 and 44 kDa OMPs and showed reduced uptake of carbapenems, although this promoted resistance only when a carbapenemase was also present. We conclude that the imipenem-selected mutant owed its resistance to some factor other than porin loss, probably to a lesion in penicillin-binding protein 2.
奇异变形杆菌的亚胺培南耐药突变体缺乏一种26 kDa的外膜蛋白（OMP）。此前曾推测该蛋白是一种孔蛋白，但目前这个对美西林交叉耐药但对其他β-内酰胺类药物不耐药的突变体，对碳青霉烯类药物的通透性与其亲本相同。一个美西林筛选出的突变体具有类似的交叉耐药性，但保留了26 kDa的OMP，证实该蛋白对耐药性并不重要。相比之下，头孢西丁筛选出的突变体保留了26 kDa的蛋白，但主要的41 kDa和44 kDa OMP的表达减少，并且对碳青霉烯类药物的摄取减少，尽管只有当同时存在碳青霉烯酶时才会促进耐药性。我们得出结论，亚胺培南筛选出的突变体的耐药性归因于除孔蛋白缺失之外的某些因素，可能是青霉素结合蛋白2的损伤。
