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分枝杆菌的蛋氨酸亚砜还原酶 B(MsrB)在抵抗氧化应激方面发挥的作用有限。

Methionine sulfoxide reductase B (MsrB) of Mycobacterium smegmatis plays a limited role in resisting oxidative stress.

机构信息

Department of Microbiology and Immunology and Regional Academic Health Center, University of Texas Health Science Center at San Antonio, Edinburg, TX 78541, USA.

出版信息

Tuberculosis (Edinb). 2009 Dec;89 Suppl 1(Suppl 1):S26-32. doi: 10.1016/S1472-9792(09)70008-3.

Abstract

Pathogenic mycobacteria including Mycobacterium tuberculosis resists phagocyte generated reactive oxygen intermediates (ROI) and this constitutes an important virulence mechanism. We have previously reported, using Mycobacterium smegmatis as a model to identify the bacterial components that resist intracellular ROI, that an antioxidant methionine sulfoxide reductase A (MsrA) plays a critical role in this process. In this study, we report the role of methionine sulfoxide reductase B (MsrB) in resistance to ROI by constructing a msrB mutant (MSDeltamsrB) and MsrA/B double mutant (MSDeltamsrA/B) strains of M. smegmatis and testing their survival in unactivated and interferon gamma activated mouse macrophages. WhilemsrB mutant exhibited significantly lower intracellular survival than its wild type counterpart, the survival rate seemed to be much higher than msrA mutant (MSDeltamsrA) strain. Further, the msrB mutant showed no sensitivity to oxidants in vitro. The msrA/B double mutant (MSDeltamsrA/B), on the other hand, exhibited a phenotype similar to that of msrA mutant in terms of both intracellular survival and sensitivity to oxidants. We conclude, therefore, that MsrB of M. smegmatis plays only a limited role in resisting intracellular and in vitro ROI.

摘要

包括结核分枝杆菌在内的致病性分枝杆菌能够抵抗吞噬细胞产生的活性氧中间体(ROI),这是一种重要的毒力机制。我们之前曾报道过,使用耻垢分枝杆菌作为模型来鉴定抵抗细胞内 ROI 的细菌成分,发现一种抗氧化的甲硫氨酸亚砜还原酶 A(MsrA)在这个过程中起着关键作用。在这项研究中,我们通过构建 msrB 突变体(MSDeltamsrB)和 MsrA/B 双突变体(MSDeltamsrA/B)来研究甲硫氨酸亚砜还原酶 B(MsrB)在抵抗 ROI 中的作用,并检测它们在未激活和干扰素 γ 激活的小鼠巨噬细胞中的存活情况。虽然 msrB 突变体的细胞内存活率明显低于其野生型,但存活率似乎比 msrA 突变体(MSDeltamsrA)菌株高得多。此外,msrB 突变体在体外对氧化剂没有敏感性。另一方面,msrA/B 双突变体(MSDeltamsrA/B)在细胞内存活和对氧化剂的敏感性方面表现出与 msrA 突变体相似的表型。因此,我们得出结论,耻垢分枝杆菌的 MsrB 仅在抵抗细胞内和体外 ROI 方面发挥有限作用。

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