CAJ | 학술논문

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 30.5×103～33.5×103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CIA结合PBP进而破坏Hp细胞壁有关.
목적 탐토극랍유산(CLA)강저유문라간균(Hp)대갑초서(MZ)내약성적체외작용급궤제.방법 유위경활검표본분리배양11주Hp균주,통과수궤확증적DNA다태성분석학정균주위불동래원.응용경지희석법급E-TEST검측CLA여MZ대Hp적최저억균농도(MIC).응용투사전경법급청매소결합단백(PBP)경쟁성결합억제실험탐토CLA대Hp적작용궤제.결과 재11주불동래원적Hp균주,1×MIC농도적CLA가명현개선MZ내약균주적MIC치(1.442±0.459비0.376±0.288,P=0.0077),사MZ내약균주전변위민감균주.CLA가여Hp 30.5×103～33.5×103적PBP결합,사Hp발생구형변、공포양변,세포벽파렬급용균.결론 CLA재체외가강저Hp대MZ적내약성,기궤제가능여CIA결합PBP진이파배Hp세포벽유관.
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 endoscopically 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 Epailometer test (E-test). The effect of CLA on the morphology of Hp was examined by transmission electron microscopy. Fluorescein-C6-aminopenicillanic 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(30.5-33.5×103). Conclusions CLA suppresses the antibiotic resistance of Hp to MZ through its binding with PBPs which results in the morphology changes of Hp.