Two Amino Acids Mutation of Ferric Uptake Regulator Determines Helicobacter pylori Resistance to Metronidazole
Two Amino Acids Mutation of Ferric Uptake Regulator Determines Helicobacter pylori Resistance to Metronidazole
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DOI：
10.1089/ars.2010.3146
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发表时间：
2011-01-01
影响因子：
6.6
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
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作者：
Tsugawa, Hitoshi;Suzuki, Hidekazu;Hibi, Toshifumi
甲硝唑（Mtz）是一种前药，当其硝基被还原并产生超氧自由基时，可转化为其活性形式。超氧自由基对细菌有直接毒性。另一方面，幽门螺杆菌的转录调节因子铁摄取调节因子（Fur）是铁辅因子超氧化物歧化酶SodB的直接抑制因子，其对于保护免受超氧化物攻击是必需的。在这里，我们证明，在一些Mtz耐药菌株，SodB活性诱导剂量依赖性的方式暴露于Mtz。此外，在Mtz暴露下，在Mtz抗性菌株中的超氧自由基的产生显着减少相比，在Mtz敏感菌株。结果表明，这些耐Mtz菌株均携带有Fur基因的C78 Y、P114 S突变（突变型Fur）。的music型Fur的结合亲和力的操纵子序列上的sodB启动子（Fur-Box）显着降低。我们的方法表明，SodB的表达是去抑制的muplant型毛皮，这是与Mtz抗性的发展。抗氧化剂。氧化还原信号。14，15-23。
Metronidazole (Mtz) is a prodrug that is converted to its active form when its nitro group is reduced and superoxide radicals are generated. The superoxide radicals are directly toxic to the bacterium. On the other hand, the transcriptional regulator, ferric uptake regulator (Fur), of Helicobacter pylori is a direct suppressor of the iron-cofactored superoxide dismutase SodB, which is essential for protection against superoxide attack. Here, we demonstrate that in some Mtz-resistant strains, SodB activity is induced in a dose-dependent manner on exposure to Mtz. Further, under Mtz exposure, the generation of superoxide radicals in Mtz-resistant strains was significantly reduced as compared with that in the Mtz-susceptible strains. These Mtz-resistant strains were found to carry amino acids mutation of Fur (C78Y, P114S; mutant-type Fur). The binding affinity of the mutant-type Fur to an operator sequence on the sodB promoter (Fur-Box) was significantly reduced. Our approach demonstrated that SodB expression is derepressed by mutant-type Fur, which is associated with the development of Mtz resistance. Antioxid. Redox Signal. 14, 15-23.