Abstract
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.
Highlights
Staphylococcus aureus is a human pathogen that causes several diseases such as suppurative diseases, food poisoning and toxic shock syndrome [1, 2]
We investigated the susceptibility of an srrA-inactivated TY34 mutant to S. sanguinis and found that the mutant had a small inhibition zone compared with the WT (Fig 1C)
We demonstrated in this study that an srrA-inactivated mutant has a smaller inhibition zone surrounding S. sanguinis than does the WT by a direct assay and that this inhibition was completely relieved by anaerobic incubation or catalase treatment (Fig 1)
Summary
Staphylococcus aureus is a human pathogen that causes several diseases such as suppurative diseases, food poisoning and toxic shock syndrome [1, 2]. Viridans group streptococci produced H2O2 and had an antagonistic effect on pathogens [13,14,15]. Streptococcus sanguinis is an oral bacterium that is found primarily in dental plaques and has been reported to be an H2O2-producing species. Several reports have demonstrated that the H2O2 produced by S. sanguinis can kill other oral bacterial species [18, 19]. Uehara et al reported that viridans group streptococci containing S. sanguinis inhibit colonization with S. aureus in newborns, which has been attributed to H2O2 [20, 21]. S. aureus was reported to possess several factors that confer resistance to H2O2, such as catalase (KatA), alkyl hydroperoxide reductase (AhpC) and DNA-binding proteins from starved cells (Dps) [22,23,24]. The biological relevance of interactions between S. sanguinis, a resident of the oral cavity, and S. aureus is uncertain
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