Contribution of Coagulase and Its Regulator SaeRS to Lethality of CA-MRSA 923 Bacteremia

Coagulase is a critical factor for distinguishing Staphylococcus aureus and coagulase-negative Staphylococcus. Our previous studies demonstrated that the null mutation of coagulase (coa) or its direct regulator, SaeRS, significantly enhanced the ability of S. aureus (CA-MRSA 923) to survive in human blood in vitro. This led us to further investigate the role of coagulase and its direct regulator, SaeRS, in the pathogenicity of CA-MRSA 923 in bacteremia during infection. In this study, we found that the null mutation of coa significantly decreased the mortality of CA-MRSA 923; moreover, the single null mutation of saeRS and the double deletion of coa/saeRS abolished the virulence of CA-MRSA 923. Moreover, the mice infected with either the saeRS knockout or the coa/saeRS double knockout mutant exhibited fewer histological lesions and less neutrophils infiltration in the infected kidneys compared to those infected with the coa knockout mutant or their parental control. Furthermore, we examined the impact of coa and saeRS on bacterial survival in vitro. The null mutation of coa had no impact on bacterial survival in mice blood, whereas the deletion mutation of saeRS or coa/saeRS significantly enhanced bacterial survival in mice blood. These data indicate that SaeRS plays a key role in the lethality of CA-MRSA 923 bacteremia, and that coagulase is one of the important virulence factors that is regulated by SaeRS and contributes to the pathogenicity of CA-MRSA 923.