摘要
目的探讨克拉维酸（CLA）降低幽门螺杆菌（Hp）对甲硝唑（MZ）耐药性的体外作用及机制。方法由胃镜活检标本分离培养11株Hp菌株，通过随机扩增的DNA多态性分析确定菌株为不同来源。应用琼脂稀释法及E—TEST检测CLA与MZ对Hp的最低抑菌浓度（MIC）。应用透射电镜法及青霉素结合蛋白（PBP）竞争性结合抑制实验探讨CLA对Hp的作用机制。结果在11株不同来源的Hp菌株，1×MIC浓度的CLA可明显改善MZ耐药菌株的MIC值（1．442±0．459比0．376±0．288，P=0．0077），使MZ耐药菌株转变为敏感菌株。CLA可与Hp 30．5×10^3～33．5×10^3的PBP结合，使Hp发生球形变、空泡样变，细胞壁破裂及溶菌。结论CLA在体外可降低Hp对MZ的耐药性，其机制可能与CLA结合PBP进而破坏Hp细胞壁有关。
Objective To elucidate the effect of clavulanic acid （CLA） in suppressing the antibiotic resistance of Helicobacter pylori （Hp） to metronidazole （MZ） and its mechanism. Methods All Hp strains were isolated from biopsy specimens taken endoscopieally and random amplified polymorphic DNA assay （RAPD） was used to certificate the distinct origin of these strains. The minimum inhibitory concentration （MIC） of CLA and MZ aganst Hp were determined by using agar dilution procedure and Epsilometer test （E test）. The effect of CLA on the morphology of Hp was examined by transmission electron microscopy. Fluorescein-C6-aminopeniciltanic acid （FLU-C6-APA） competition assay was used to detect the binding between CLA and penicillin-binding proteins （PBPs）. Results Eleven strains were isolated. In vitro CLA could decrease the MIC of MZ resistant（ 1. 442 ±0. 459 vs 0. 376±0. 288, P= 0. 0077）, but not affect the MIC for MZ sensitive strains significantly （P 〉 0. 05）. Exposure to CLA resulted in morphological changes of Hp, including cell wall disintegration and cell lysis. Furthermore, CLA inhibited the binding of FLU-C6-APA to PBPs（30.5-33.5 ×10^3 ） . Conclusions CLA suppresses the antibiotic resistance of Hp to MZ through its binding with PBPs which results in the morphology changes of Hp.
出处
《中华消化杂志》
CAS
CSCD
北大核心
2008年第9期608-611,共4页
Chinese Journal of Digestion
基金
上海市科委自然科学基金资助项目（04ZR14065）,上海第二医科大学自然科学基金资助项目（04XJ-21101）
关键词
克拉维酸
幽门螺杆菌
甲硝唑
细菌敏感实验
Clavulanic acid
Helicobacter pylori
Metronidazole
Microbial sensitivity tests
