The effect of clavulanic acid in suporessing the antibiotic resistance of Helicobacter pylori to metronidazole / 中华消化杂志

ABSTRACT

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.