Contribution of a LysM domain-containing protein regulated by VicRK to <i>Streptococcus sanguinis</i> virulence
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<i>Streptococcus sanguinis</i> is a commensal member of the oral microbiome involved in opportunistic cardiovascular infections. In the present study, we investigated the contribution of <i>ssa_0094</i>, a gene strongly regulated by the two-component system VicRK, to functions associated with biofilm formation, immune evasion, and cardiovascular virulence. <i>In silico</i> analysis showed that <i>ssa_0094</i> encodes a protein with a LysM domain, which is highly conserved among <i>S. sanguinis</i>. Although not an ubiquitous gene, several commensal streptococcal species of the oronasopharynx and zoonotic strains of <i>Streptococcus suis</i> harbor <i>ssa_0094</i> homologues. A <i>ssa_0094</i> isogenic mutant (SK0094) showed defects in initiating biofilms on saliva-coated surfaces, reduced hydrophobicity, and lower production of amyloid-like components when compared to the parent strain (SK36) or to the complemented mutant (SK0094+), although it showed mild changes in DNA release and production of H<sub>2</sub>O<sub>2</sub>. Deletion of <i>ssa_0094</i> also impaired <i>S. sanguinis</i> binding to multiple human glycoproteins of plasma and/or extracellular matrix (ECM) (plasminogen, fibronectin, fibrinogen, fibrin, type I collagen, and elastin) and promoted clear increases in C3b deposition and in induction of NEtosis by neutrophils of peripheral blood. Moreover, SK0094 showed impaired invasiveness into HCAEC cells and reduced <i>ex vivo</i> persistence in human blood, but no clear change in virulence in a <i>Galleria mellonella</i> infection model. These findings indicate that <i>ssa_0094</i> is highly conserved within <i>S. sanguinis</i> strains and required for biofilm initiation as well as for multiple functions of immune evasion and cardiovascular virulence in <i>S. sanguinis</i> in a host-specific fashion.
