The SaeRS Two-Component System Controls Survival of Staphylococcus aureus in Human Blood through Regulation of Coagulase.

Haiyong Guo,Yinduo Ji,Jeffrey W Hall,Junshu Yang

doi:10.3389/fcimb.2017.00204

Haiyong Guo, Yinduo Ji + Show 2 more

Open Access

https://doi.org/10.3389/fcimb.2017.00204

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Abstract

The SaeRS two-component system plays important roles in regulation of key virulence factors and pathogenicity. In this study, however, we found that the deletion mutation of saeRS enhanced bacterial survival in human blood, whereas complementation of the mutant with SaeRS returned survival to wild-type levels. Moreover, these phenomena were observed in different MRSA genetic background isolates, including HA-MRSA WCUH29, CA-MRSA 923, and MW2. To elucidate which gene(s) regulated by SaeRS contribute to the effect, we conducted a series of complementation studies with selected known SaeRS target genes in trans. We found coagulase complementation abolished the enhanced survival of the SaeRS mutant in human blood. The coa and saeRS deletion mutants exhibited a similar survival phenotype in blood. Intriguingly, heterologous expression of coagulase decreased survival of S. epidermidis in human blood. Further, the addition of recombinant coagulase to blood significantly decreased the survival of S. aureus. Further, analysis revealed staphylococcal resistance to killing by hydrogen peroxide was partially dependent on the presence or absence of coagulase. Furthermore, complementation with coagulase, but not SaeRS, returned saeRS/coa double mutant survival in blood to wild-type levels. These data indicate SaeRS modulates bacterial survival in blood in coagulase-dependent manner. Our results provide new insights into the role of staphylococcal SaeRS and coagulase on bacterial survival in human blood.

Highlights

Staphylococcus aureus is an important pathogen that can cause various infections, including skin and soft tissue infection and systematic infections such as pneumoniae, endocarditis, and toxic shock syndrome (Klevens et al, 2007; Gordon and Lowy, 2008)
Our previous studies have demonstrated that the AirSR(YhcSR) system contributes S. aureus survival in human blood (Hall et al, 2015, 2017); and our preliminary study found that AirSR probably positively regulates the transcription of saeRS
Our results clearly indicate the roles of SaeRS and coagulase in S. aureus survival in human blood

Summary

Introduction

Staphylococcus aureus is an important pathogen that can cause various infections, including skin and soft tissue infection and systematic infections such as pneumoniae, endocarditis, and toxic shock syndrome (Klevens et al, 2007; Gordon and Lowy, 2008). Two-component signal regulatory systems (TCSs) collaborate with transcriptional regulators to regulate the expression of virulence factors, which in turn contribute to the pathogenesis of Effect of SaeRS on S. aureus Survival. SaeRS up-regulates the transcription and expression of hla, hlb, hlgABC, lukED, and coa in vitro (Giraudo et al, 1999; Liang et al, 2006; Rogasch et al, 2006; Nygaard et al, 2010), as well as controls hla expression in vivo, as the sae null mutation significantly decreased the expression of α-toxin (hla) during infection (Goerke et al, 2001, 2005). It has been demonstrated that the SaeRS system is an important virulence regulator in various animal models of infection (Goerke et al, 2005; Liang et al, 2006; Voyich et al, 2009; Montgomery et al, 2010; Cho et al, 2015; Zhao et al, 2015)

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