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首页> 外文期刊>Infection and immunity >Role of Methionine Sulfoxide Reductases A and B of Enterococcus faecalis in Oxidative Stress and Virulence
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Role of Methionine Sulfoxide Reductases A and B of Enterococcus faecalis in Oxidative Stress and Virulence

机译:粪肠球菌蛋氨酸亚砜还原酶A和B在氧化应激和毒力中的作用

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Methionine sulfoxide reductases A and B are antioxidant repair enzymes that reduce the S- and R-diastereomers of methionine sulfoxides back to methionine, respectively. Enterococcus faecalis, an important nosocomial pathogen, has one msrA gene and one msrB gene situated in different parts of the chromosome. Promoters have been mapped and mutants have been constructed in two E. faecalis strains (strains JH2-2 and V583) and characterized. For both backgrounds, the mutants are more sensitive than the wild-type parents to exposure to H2O2, and in combination the mutations seem to be additive. The virulence of the mutants has been analyzed in four different models. Survival of the mutants inside mouse peritoneal macrophages stimulated with recombinant gamma interferon plus lipopolysaccharide but not in na?ve phagocytes is significantly affected. The msrA mutant is attenuated in the Galleria mellonella insect model. Deficiency in either Msr enzyme reduced the level of virulence in a systemic and urinary tract infection model. Virulence was reconstituted in the complemented strains. The combined results show that Msr repair enzymes are important for the oxidative stress response, macrophage survival, and persistent infection with E. faecalis.
机译:甲硫氨酸亚砜还原酶A和B是抗氧化剂修复酶,它们分别将甲硫氨酸亚砜的S-和R-非对映异构体还原成蛋氨酸。粪肠球菌是一种重要的医院病原体,在染色体的不同部分具有一个msrA基因和一个msrB基因。已经绘制了启动子并在两个粪肠球菌菌株(菌株JH2-2和V583)中构建了突变体并进行了表征。对于这两种背景,这些突变体都比野生型亲本对暴露于H2O2更为敏感,并且组合起来,这些突变似乎是累加的。已在四种不同模型中分析了突变体的毒力。重组γ干扰素加脂多糖刺激的小鼠腹膜巨噬细胞内突变体的存活受到了显着影响,但未在幼稚的吞噬细胞中存活。在Malleria mellonella昆虫模型中,msrA突变体减毒。两种Msr酶的缺乏都会降低全身性和尿路感染模型中的毒力水平。毒力在补充菌株中重建。综合结果表明,Msr修复酶对于氧化应激反应,巨噬细胞存活和粪肠球菌的持续感染非常重要。

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