Silkworm Apolipophorin Protein Inhibits Hemolysin Gene Expression of Staphylococcus aureus via Binding to Cell Surface Lipoteichoic Acids

We previously reported that a silkworm hemolymph protein, apolipophorin (ApoLp), binds to the cell surface of Staphylococcus aureus and inhibits expression of the saePQRS operon encoding a two-component system, SaeRS, and hemolysin genes. In this study, we investigated the inhibitory mechanism of ApoLp on S. aureus hemolysin gene expression. ApoLp bound to lipoteichoic acids (LTA), an S. aureus cell surface component. The addition of purified LTA to liquid medium abolished the inhibitory effect of ApoLp against S. aureus hemolysin production. In an S. aureus knockdown mutant of ltaS encoding LTA synthetase, the inhibitory effects of ApoLp on saeQ expression and hemolysin production were attenuated. Furthermore, the addition of anti-LTA monoclonal antibody to liquid medium decreased the expression of S. aureus saeQ and hemolysin genes. In S. aureus strains expressing SaeS mutant proteins with a shortened extracellular domain, ApoLp did not decrease saeQ expression. These findings suggest that ApoLp binds to LTA on the S. aureus cell surface and inhibits S. aureus hemolysin gene expression via a two-component regulatory system, SaeRS. Background: Silkworm ApoLp protein binds S. aureus cell surfaces and inhibits hemolysin gene expression. Results: ApoLp protein binds LTA. The ApoLp inhibitory effect was attenuated in an LTA synthetase knockdown mutant. Conclusion: ApoLp protein suppressed S. aureus virulence via LTA binding. Significance: A non-protein macromolecule on the bacterial cell surface functions as a receptor in the bacterial signal transduction pathway.