OsmC proteins of Mycobacterium tuberculosis and Mycobacterium smegmatis protect against organic hydroperoxide stress.
OsmC proteins of Mycobacterium tuberculosis and Mycobacterium smegmatis protect against organic hydroperoxide stress.
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DOI：
10.1016/j.tube.2011.10.021
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发表时间：
2011-12
期刊：
影响因子：
--
通讯作者：
Dhandayuthapani S
中科院分区：
文献类型：
--
作者：
Saikolappan S;Das K;Sasindran SJ;Jagannath C;Dhandayuthapani S
在宿主-病原体相互作用过程中，细菌抗氧化剂在内源性和宿主来源的氧化自由基解毒中起着关键作用。近年来，渗透诱导细菌蛋白C （OsmC）因其与有机氢过氧化物还原酶（Ohr）具有结构和功能上的关系而被纳入抗氧化酶的范畴。编码OsmC的基因拷贝在分枝杆菌物种中是保守的，包括结核分枝杆菌（Rv2923c）和耻垢分枝杆菌（MSMEG2421），但其在保护这些物种免受氧化应激中的作用尚不清楚。为了确定OsmC在分枝杆菌氧化应激中的作用，我们过度表达和纯化了结核分枝杆菌和垢垢分枝杆菌的OsmCs，并在二甲醇亚铁离子氧化（FOX）试验中评估了它们还原过氧化氢（H2O2）、过氧化氢异丙烯（CHP）和过氧化氢t-丁基（t-BHP）等过氧化底物的能力。这表明两个物种的OsmCs都能够还原无机（H2O2）和有机（CHP和t-BHP）过氧化物。此外，与亲本野生型菌株相比，缺乏OsmC的垢垢分枝杆菌突变体（MSΔosmC）的CHP和t-BHP降低，表明OsmC蛋白对分枝杆菌总过氧化物还原酶活性有重要作用。MSΔosmC菌株对有机氢过氧化物也很敏感，这可以通过与质粒携带的osmC互补来逆转。质粒携带的osmC也增加了耻垢分枝杆菌野生型菌株对异烟肼（INH）的抗性，但其抗性水平相对低于有机氢过氧化物还原酶ahpC。这些结果表明OsmC在过氧化物代谢和保护分枝杆菌抗氧化应激中起重要作用。
Bacterial antioxidants play a critical role in the detoxification of endogenously and host derived oxidative radicals during host-pathogen interactions. Recently, the osmotically induced bacterial protein C (OsmC) is included in the antioxidant category of enzymes as it shows structural and functional relationships with organic hydroperoxide reductase (Ohr) enzyme. A copy of the gene encoding OsmC is conserved across mycobacterial species, including Mycobacterium tuberculosis (Rv2923c) and M. smegmatis (MSMEG2421), but its role in protecting these species against oxidative stress is unknown. To determine the role of OsmC in mycobacterial oxidative stress, we overexpressed and purified OsmCs of M. tuberculosis and M. smegmatis and assessed their ability to reduce peroxide substrates like hydrogen peroxide (H2O2), cumene hydroperoxide (CHP) and t-butyl hydroperoxide (t-BHP) in Ferrous Ion Oxidation in Xylenol (FOX) assay. This revealed that OsmCs from both species were capable of reducing both inorganic (H2O2) and organic (CHP and t-BHP) peroxides. Further, an M. smegmatis mutant (MSΔosmC) deficient in OsmC exhibited reduced reduction of CHP and t-BHP than the parental wild type strain, indicating that OsmC protein contributes significantly for the total peroxide reductase activity of mycobacteria. The MSΔosmC strain was also sensitive to organic hydroperoxides, which could be reversed by complementing with a plasmid borne osmC. Plasmid borne osmC also increased the resistance of M. smegmatis wild type strain to isoniazid (INH) but at a relatively lower level than ahpC, an organic hydroperoxide reductase. These results suggest that OsmC plays an important role in peroxide metabolism and protecting mycobacteria against oxidative stress.
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影响因子：
11.4
作者：
Lesniak, J;Barton, WA;Nikolov, DB
通讯作者：
Nikolov, DB
DOI：
10.1073/pnas.0505446102
发表时间：
2005-08-23
影响因子：
11.1
作者：
Morris, RP;Nguyen, L;Thompson, CJ
通讯作者：
Thompson, CJ
影响因子：
3.6
作者：
Gordia, S;Gutierrez, C
通讯作者：
Gutierrez, C
影响因子：
3.6
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
通讯作者：
Nathan C
影响因子：
2.8
作者：
Master, SS;Springer, B;Timmins, GS
通讯作者：
Timmins, GS