Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates
Frameshift mutations in rdxA and metronidazole resistance in North American Helicobacter pylori isolates
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DOI：
10.1093/jac/46.5.793
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发表时间：
2000-11-01
影响因子：
5.2
通讯作者：
Versalovic, J
中科院分区：
文献类型：
--
作者：
Kwon, DH;Peña, JA;Versalovic, J
在幽门螺杆菌中，氧不敏感的硝基还原酶RdxA可能通过还原和形成细胞毒性中间体来激活甲硝唑（Mtz）。rdxA突变与幽门螺杆菌的Mtz耐药有关。采用琼脂稀释法测定了17株幽门螺杆菌的体外Mtz敏感性。8株敏感菌株（MIC范围：0.25 ~ 1.0 mg/L）和9株耐药菌株（MIC范围：16 ~ 256 mg/L）的rdxA等位基因DNA序列分析显示，9株耐药菌株中有6株含有插入或缺失突变（‘indel’突变）。一个分离物在密码子位置148处包含一个取代突变，导致过早引入终止密码子。移码突变或替换突变在rdxA编码序列中产生终止密码子，导致翻译过早终止和推定截断的rdxA多肽的表达。
In Helicobacter pylori, the oxygen-insensitive nitroreductase RdxA is likely to activate metronidazole (Mtz) by reduction and formation of cytotoxic intermediates. Mutations in rdxA have been associated with Mtz resistance in H. pylori. In vitro Mtz susceptibilities of 17 randomly selected H. pylori isolates were determined by the agar dilution method. DNA sequence analysis of rdxA alleles of eight susceptible isolates (MIC range: 0.25-1.0 mg/L) and nine resistant isolates (MIC range: 16-256 mg/L) showed that six of nine Mtz-resistant H. pylori isolates contained insertion or deletion mutations ('indel' mutations). One isolate contained a substitution mutation at codon position 148 that resulted in the introduction of a premature stop codon. Creation of stop codons within the rdxA coding sequence by either frameshift or substitution mutations resulted in premature translation termination and expression of putatively truncated RdxA polypeptides.