Mycobacterium tuberculosis expresses methionine sulphoxide reductases A and B that protect from killing by nitrite and hypochlorite.

Mycobacterium tuberculosis expresses methionine sulphoxide reductases A and B that protect from killing by nitrite and hypochlorite.
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DOI:
10.1111/j.1365-2958.2008.06548.x
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发表时间:
2009-02
影响因子:
3.6
通讯作者:
Nathan C
Nathan C
中科院分区:
生物学2区
文献类型:
--
作者:
Lee WL;Gold B;Darby C;Brot N;Jiang X;de Carvalho LP;Wellner D;St John G;Jacobs WR Jr;Nathan C

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蛋氨酸亚砜还原酶(Msr 's)将蛋氨酸亚砜还原为蛋氨酸,保护细菌免受活性氧中间体(ROI)和活性氮中间体(RNI)的侵害。许多生物体同时表达对蛋氨酸-(S)-亚砜有活性的MsrA和对蛋氨酸-(R)-亚砜有活性的MsrB。结核分枝杆菌(Mtb)表达MsrA,它保护ΔmsrA-E。ROI和RNI的大肠杆菌。然而,MsrA在Mtb中的作用尚未明确,Mtb是否表达MsrB尚不清楚。我们确定MsrB是由Rv2674在Mtb中编码的蛋白,并证实重组Mtb MsrA和MsrB具有明显的立体特异性。我们产生了MsrA、MsrB或两者都缺乏的结核分枝杆菌菌株,并对突变体进行了补充。单缺陷菌株的裂解物对n -乙酰蛋氨酸亚砜的Msr活性为野生型的一半。然而,与其他细菌相比,单突变体并不比野生型更容易被ROI/RNI杀死。只有同时缺乏MsrA和MsrB的Mtb更容易被亚硝酸盐或次氯酸盐杀死。因此,MsrA和MsrB有助于Mtb对ROI和RNI的酶防御。
Methionine sulfoxide reductases (Msr’s) reduce methionine sulfoxide to methionine and protect bacteria against reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI). Many organisms express both MsrA, active against methionine-(S)-sulfoxide, and MsrB, active against methionine-(R)-sulfoxide. Mycobacterium tuberculosis (Mtb) expresses MsrA, which protects ΔmsrA-E. coli from ROI and RNI. However, the function of MsrA in Mtb has not been defined, and it is unknown whether Mtb expresses MsrB. We identified MsrB as the protein encoded by Rv2674 in Mtb and confirmed the distinct stereospecificities of recombinant Mtb MsrA and MsrB. We generated strains of Mtb deficient in MsrA, MsrB or both and complemented the mutants. Lysates of singly deficient strains displayed half as much Msr activity as wild type against N-acetyl methionine sulfoxide. However, in contrast to other bacteria, single mutants were no more vulnerable than wild type to killing by ROI/RNI. Only Mtb lacking both MsrA and MsrB was more readily killed by nitrite or hypochlorite. Thus, MsrA and MsrB contribute to the enzymatic defenses of Mtb against ROI and RNI.
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