The MsrAB reducing pathway of Streptococcus gordonii is needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice

The ability of Streptococcus gordonii to cope with oxidative stress is important for survival and persistence in dental plaque. In this study, we used mutational, phenotypic, and biochemical approaches to characterize the role of a methionine sulfoxide reductase (MsrAB) and proteins encoded by genes in the msrAB operon and an adjacent operon in oxidative stress tolerance in S. gordonii. The results showed that MsrAB and four other proteins encoded in the operons are needed for protection from H2O2 and methionine sulfoxide. These five proteins formed a reducing pathway that was needed for oxidative stress tolerance, biofilm formation, and oral colonization in mice. In the pathway, MsrAB was the enzyme that repaired oxidatively damaged proteins, and the two thioredoxin-like lipoproteins (SdbB and Sgo_1177) and two CcdA proteins were proteins that maintained the catalytic cycle of MsrAB. Consistent with the role in oxidative stress tolerance, the production of MsrAB, SdbB, and Sgo_11777 was induced in aerobic growth and planktonic cells.戈登链球菌（Streptococcus gordonii）应对氧化应激的能力对于其在牙菌斑中的存活与持续定植至关重要。本研究采用突变、表型及生化实验手段，表征了蛋氨酸亚砜还原酶（MsrAB）以及msrAB操纵子与相邻操纵子编码的蛋白在戈登链球菌氧化应激耐受中的作用。研究结果显示，MsrAB及该操纵子编码的另外四种蛋白可帮助菌体抵御过氧化氢与蛋氨酸亚砜造成的损伤。这五种蛋白构成一条还原通路，该通路对于菌体的氧化应激耐受、生物膜形成以及小鼠口腔定植均不可或缺。在该通路中，MsrAB负责修复氧化损伤的蛋白，而两种硫氧还蛋白样脂蛋白（SdbB与Sgo_1177）以及两种CcdA蛋白则负责维持MsrAB的催化循环。与氧化应激耐受的功能相一致，在需氧生长及浮游态菌体中，MsrAB、SdbB与Sgo_11777的表达会被诱导上调。