幽门螺杆菌根除失败后甲硝唑耐药机制的研究

Mechanism of metronidazole resistance after failed eradication of Helicobacter pylori

目的探讨幽门螺杆菌(Hp)根除失败后甲硝唑的耐药机制。方法通过纸片扩散法选取原始敏感菌株、原始耐药菌株及根除治疗失败后的Hp耐药菌株;从原始敏感菌株、原始耐药菌株及根除治疗失败后的Hp耐药菌株扩增rdxA基因,聚合酶链式反应(PCR)产物进行DNA测序以探讨甲硝唑耐药机制。结果将甲硝唑的原始敏感菌株、原始耐药菌株、根除失败后耐药菌株的rdxA基因与标准菌株进行对比,核苷酸同源性较高(P>0.05);氨基酸同源性分析示,原始耐药菌株的氨基酸同源性低于原始敏感菌株和根除失败后的耐药菌株(P<0.05)。结论 rdxA基因突变可能是甲硝唑原始耐药菌株产生耐药性的主要原因,但是根除失败后甲硝唑耐药菌株耐药性的产生可能还有其他原因。

Objective To explore the mechanism of metronidazole resistance after failed eradication of Helicobacter pylori（HP）. Methods Disk diffusion test was used to select the primary sensitive HP strains （ MTZ^s ）, primary resistant HP strains （ MTZ^R） and post-failure resistant HP strains. The rdxA gene fragment was amplified by PCR from primary MTZs strains, primary MTZ^R strains and post-failure MTZ^R strains. PCR products were sequenced to explore the mechanism of metronidazole resistance. Results Comparison of rdxA genes from primary MTZs strains, primary MTZ^R strains and post-failure MTZ^R strains with standard strains showed a high homology in DNA （P 〉0. 05）. Lower homology in amino acids was shown in primary MTZ^R was than in primary MTZs and post- failure MTZ^R （P 〈 0. 05）. Conclusion rdxA gene mutation may be the major factor contributing to primary resistance,although others can be involved in mechanism of metrenidazole resistance after failed eradication of HP.