<i>Staphylococcus aureus</i> SrrAB Affects Susceptibility to Hydrogen Peroxide and Co-Existence with <i>Streptococcus sanguinis</i>

Staphylococcus aureus is a pathogen and a commensal bacterial species that is found in humans. Bacterial two-component systems (TCSs) sense and respond to environmental stresses, which include antimicrobial agents produced by other bacteria. In this study, we analyzed the relation between the TCS SrrAB and susceptibility to the hydrogen peroxide (H2O2) that is produced by Streptococcus sanguinis, which is a commensal oral streptococcus. An srrA-inactivated S. aureus mutant demonstrated low susceptibility to the H2O2 produced by S. sanguinis. We investigated the expression of anti-oxidant factors in the mutant. The expression of katA in the mutant was significantly higher than in the wild-type (WT) in the presence or absence of 0.4 mM H2O2. The expression of dps in the mutant was significantly increased compared with the WT in the presence of H2O2 but not in the absence of H2O2. A katA or a dps-inactivated mutant had high susceptibility to H2O2 compared with WT. In addition, we found that the nitric oxide detoxification protein (flavohemoglobin: Hmp), which is regulated by SrrAB, was related to H2O2 susceptibility. The hmp-inactivated mutant had slightly lower susceptibility to the H2O2 produced by S. sanguinis than did WT. When a srrA-inactivated mutant or the WT were co-cultured with S. sanguinis, the population percentage of the mutant was significantly higher than the WT. In conclusion, SrrAB regulates katA, dps and hmp expression and affects H2O2 susceptibility. Our findings suggest that SrrAB is related in vivo to the co-existence of S. aureus with S. sanguinis.金黄色葡萄球菌（Staphylococcus aureus）是一种可在人体中定植的病原菌与共生细菌。细菌双组分系统（two-component systems, TCSs）可感知并响应环境胁迫，包括其他细菌产生的抗菌物质。本研究分析了双组分系统SrrAB与缓症链球菌（Streptococcus sanguinis，一种共生口腔链球菌）产生的过氧化氢（H2O2）易感性之间的关联。srrA基因灭活的金黄色葡萄球菌突变株对缓症链球菌产生的H2O2敏感性显著降低。我们检测了该突变株中抗氧化因子的表达水平：在添加或不添加0.4 mM H2O2的条件下，突变株中katA的表达量均显著高于野生型（WT）；而dps的表达量仅在添加H2O2时较野生型显著升高，未添加时无明显差异。katA或dps基因灭活的突变株对H2O2的敏感性均显著高于野生型。此外，我们发现受SrrAB调控的一氧化氮解毒蛋白——黄素血红蛋白（Hmp）同样与H2O2敏感性相关：hmp基因灭活的突变株对缓症链球菌产生的H2O2敏感性略低于野生型。当srrA基因灭活的突变株或野生型与缓症链球菌共培养时，突变株的种群占比显著高于野生型。综上，SrrAB可调控katA、dps及hmp的表达，并影响菌株对H2O2的敏感性。本研究结果提示，SrrAB与金黄色葡萄球菌和缓症链球菌的体内共生过程密切相关。