Tanih N F, Ndip L M, Ndip R N
Microbial Pathogenicity and Molecular Epidemiology Research Group, Department ofBiochemistry and Microbiology, Faculty of Science and Agriculture, University of Fort Hare, Alice 5700, South Africa.
Ann Trop Med Parasitol. 2011 Apr;105(3):251-9. doi: 10.1179/136485911X12899838683485.
Helicobacter pylori has been incriminated in human diseases, such as peptic ulcer, gastritis and gastric malignancy. Although modern triple-drug regimens are usually highly effective in the treatment of H. pylori infection, the emergence of resistance to two of the most used antibiotics, metronidazole (Mtz) and clarithromycin (Cla), is a serious and increasing problem. Truncations in the rdxA and frxA genes of H. pylori are thought to be associated with Mtz resistance whereas mutations in the pathogen's 23S-ribosomal-RNA (23S-rRNA) genes are associated with Cla resistance. In a recent study, PCR and sequence analysis of the rdxA, frxA and 23S-rRNA genes were used to explore the genetic basis of resistance to Mtz and Cla in H. pylori. When 200 isolates of H. pylori from the Eastern Cape province of South Africa were tested for antibiotic susceptibility, almost all (95·5%) were found resistant to Mtz and 20·0% were found resistant to Cla. Only the Mtz-resistant isolates showed rdxA and frxA truncation. Two point mutations were detected in the 23S-rRNA genes of the Cla-resistant isolates. Many significant changes (resulting in 13 amino-acid substitutions in nine loci and truncated proteins in 14 loci) were observed in the rdxA genes of the Mtz-resistant isolates, and it appears that, compared with the rarer changes detected in frxA, such mutations may contribute more significantly to the high prevalence of Mtz resistance. To guide empiric treatment, the genotypes and antibiotic susceptibility of H. pylori in the Eastern Cape province of South Africa need to be monitored regularly.
幽门螺杆菌已被认定与人类疾病有关，如消化性溃疡、胃炎和胃癌。尽管现代三联药物疗法通常对幽门螺杆菌感染的治疗非常有效，但对两种最常用抗生素甲硝唑（Mtz）和克拉霉素（Cla）产生耐药性的情况日益严重，成为一个棘手问题。幽门螺杆菌rdxA和frxA基因的截断被认为与对Mtz的耐药性有关，而病原体23S核糖体RNA（23S-rRNA）基因的突变则与对Cla的耐药性有关。在最近的一项研究中，通过对rdxA、frxA和23S-rRNA基因进行聚合酶链反应（PCR）和序列分析，来探究幽门螺杆菌对Mtz和Cla耐药性的遗传基础。对来自南非东开普省的200株幽门螺杆菌进行抗生素敏感性测试时，几乎所有菌株（95.5%）都对Mtz耐药，20.0%对Cla耐药。只有对Mtz耐药的菌株显示出rdxA和frxA截断。在对Cla耐药的菌株的23S-rRNA基因中检测到两个点突变。在对Mtz耐药的菌株的rdxA基因中观察到许多显著变化（导致9个位点有13个氨基酸替换，14个位点有截短蛋白），而且似乎与在frxA中检测到的较少见变化相比，此类突变可能对Mtz耐药性的高流行率有更显著的影响。为指导经验性治疗，需要定期监测南非东开普省幽门螺杆菌的基因型和抗生素敏感性。
