Staphylococcus aureus sqr Encodes a Type II Sulfide:Quinone Oxidoreductase and Impacts Reactive Sulfur Speciation in Cells.
Staphylococcus aureus sqr Encodes a Type II Sulfide:Quinone Oxidoreductase and Impacts Reactive Sulfur Speciation in Cells.
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DOI：
10.1021/acs.biochem.6b00714
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发表时间：
2016-11-29
期刊：
影响因子：
2.9
通讯作者：
Giedroc DP
中科院分区：
文献类型：
--
作者：
Shen J;Peng H;Zhang Y;Trinidad JC;Giedroc DP
最近的研究表明，硫化氢（H2S）氧化是细菌抗生素耐药性和硫化物稳态的一个重要方面。主要人类病原体金黄色葡萄球菌的cst操纵子由外源H2S应激诱导，并编码参与硫化物氧化的酶，包括I组黄素蛋白二硫化物氧化还原酶硫化物：醌氧化还原酶（SQR）。在这项工作中，我们表明，S。当提供黄素腺嘌呤二核苷酸和水溶性醌受体时，金黄色葡萄球菌SQR催化硫化钠（Na 2S）的双电子氧化成硫烷硫（SO）。氰化物、亚硫酸盐和辅酶A（CoA）都能够在体外充当S 0受体。该活性需要静息酶中的C167-C344二硫键，在催化循环中具有C344过硫化物的中间性，通过硫化物反应的SQR的质谱法验证。纯化的SQR和S.金黄色葡萄球菌CstB是一种已知的Fe Ⅱ过硫化物双加氧酶-硫转移酶，也由cst操纵子编码，以CoA依赖性方式从硫化物产生硫代硫酸盐，从而证实CoASSH分别作为SQR和CstB的产物和底物的中间性。野生型、Δsqr和Δsqr：：pSQR菌株的硫代谢物谱显示Δsqr菌株中CoASSH和无机四硫化物的内源性水平显著且特异性升高。我们的结论是，SQR影响这些活性硫物种的细胞形态，但牵连其他机制不依赖于SQR的形成低分子量的硫醇过硫化物和无机多硫化物在硫化物稳态失调。
Recent studies implicate hydrogen sulfide (H2S) oxidation as an important aspect of bacterial antibiotic resistance and sulfide homeostasis. The cst operon of the major human pathogen Staphylococcus aureus is induced by exogenous H2S stress and encodes enzymes involved in sulfide oxidation, including a group I flavoprotein disulfide oxidoreductase sulfide:quinone oxidoreductase (SQR). In this work, we show that S. aureus SQR catalyzes the two-electron oxidation of sodium sulfide (Na2S) into sulfane sulfur (S0) when provided flavin adenine dinucleotide and a water-soluble quinone acceptor. Cyanide, sulfite, and coenzyme A (CoA) are all capable of functioning as the S0 acceptor in vitro. This activity requires a C167–C344 disulfide bond in the resting enzyme, with the intermediacy of a C344 persulfide in the catalytic cycle, verified by mass spectrometry of sulfide-reacted SQR. Incubation of purified SQR and S. aureus CstB, a known FeII persulfide dioxygenase-sulfurtransferase also encoded by the cst operon, yields thiosulfate from sulfide, in a CoA-dependent manner, thus confirming the intermediacy of CoASSH as a product and substrate of SQR and CstB, respectively. Sulfur metabolite profiling of wild-type, Δsqr, and Δsqr::pSQR strains reveals a marked and specific elevation in endogenous levels of CoASSH and inorganic tetrasulfide in the Δsqr strain. We conclude that SQR impacts the cellular speciation of these reactive sulfur species but implicates other mechanisms not dependent on SQR in the formation of low-molecular weight thiol persulfides and inorganic polysulfides during misregulation of sulfide homeostasis.