Functional analysis of the RdxA and RdxB nitroreductases of Campylobacter jejuni reveals that mutations in rdxA confer metronidazole resistance.
Functional analysis of the RdxA and RdxB nitroreductases of Campylobacter jejuni reveals that mutations in rdxA confer metronidazole resistance.
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对空肠弯曲杆菌 RdxA 和 RdxB 硝基还原酶的功能分析表明，rdxA 突变导致甲硝唑耐药。
DOI：
10.1128/jb.01638-09
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发表时间：
2010
影响因子：
3.2
通讯作者：
Hendrixson,DavidR
中科院分区：
文献类型：
--
作者：
Ribardo,DeborahA;Bingham-Ramos,LaceyK;Hendrixson,DavidR
空肠弯曲杆菌是人类胃肠炎的主要原因，也是许多野生和农业重要动物肠道的寄生菌。我们确定并表征了一个基因座，我们注释为rdxAB，编码两个硝基还原酶。RdxA被发现负责对甲硝唑（Mtz）的敏感性，甲硝唑是另一种epsilonproteobacterium，幽门螺杆菌的常用治疗剂。在rdxA而不是rdxB中的多个独立衍生的突变导致了对Mtz（Mtzr）的抗性，这表明，与H中的情况不同。pylori，Mtzr可能不是一个多基因性状。类似地，MtzrC. jejuni是在没有选择的情况下在体外和体内生长后分离的，其包含rdxA内的移码、点、插入或缺失突变，可能揭示了C中该性状的遗传变异性。空泡是由于细菌正常生长期间发生的自发DNA复制错误。类似于以前的研究结果与H。pyloriRdxA，C. jejuniRdxA表现出较强的氧化酶活性，只有在厌氧条件下发生的Mtz的减少。RdxB表现出类似的特征，但水平低于RdxA。遗传分析证实，rdxA和rdxB在鸡肠道内的生长过程中共转录和诱导，但这两个基因的缺失并不严重损害C。jejunian为欧洲殖民地。进一步的研究表明rdxA是一个方便的基因座互补突变体切割。我们的工作有助于不断增长的知识的决定因素，有助于敏感性Mtz（MTZS），并支持以前的意见的根本差异，从epsilonproteobacteria的硝基还原酶的活动。
Campylobacter jejuniis a leading cause of gastroenteritis in humans and a commensal bacterium of the intestinal tracts of many wild and agriculturally significant animals. We identified and characterized a locus, which we annotated asrdxAB, encoding two nitroreductases. RdxA was found to be responsible for sensitivity to metronidazole (Mtz), a common therapeutic agent for another epsilonproteobacterium,Helicobacter pylori. Multiple, independently derived mutations inrdxAbut notrdxBresulted in resistance to Mtz (Mtzr), suggesting that, unlike the case inH. pylori, Mtzrmight not be a polygenic trait. Similarly, MtzrC. jejuniwas isolated after bothin vitroandin vivogrowth in the absence of selection that contained frameshift, point, insertion, or deletion mutations withinrdxA, possibly revealing genetic variability of this trait inC. jejunidue to spontaneous DNA replication errors occurring during normal growth of the bacterium. Similar to previous findings withH. pyloriRdxA, biochemical analysis ofC. jejuniRdxA showed strong oxidase activity, with reduction of Mtz occurring only under anaerobic conditions. RdxB showed similar characteristics but at levels lower than those for RdxA. Genetic analysis confirmed thatrdxAandrdxBare cotranscribed and induced duringin vivogrowth in the chick intestinal tract, but an absence of these genes did not strongly impairC. jejunifor commensal colonization. Further studies indicate thatrdxAis a convenient locus for complementation of mutants incis. Our work contributes to the growing knowledge of determinants contributing to susceptibility to Mtz (Mtzs) and supports previous observations of the fundamental differences in the activities of nitroreductases from epsilonproteobacteria.