Association of Novel Streptococcus sanguinis Virulence Factors With Pathogenesis in a Native Valve Infective Endocarditis Model

Abstract

Streptococcus sanguinis (S. sanguinis) is an abundant oral commensal which can cause disseminated human infection if it gains access to the bloodstream. The most important among these diseases is infective endocarditis (IE). While virulence phenotypes of S. sanguinis have been correlated to disease severity, genetic factors mediating these phenotypes, and contributing to pathogenesis are largely uncharacterized. In this report, we investigate the roles of 128 genes in virulence-related phenotypes of S. sanguinis and characterize the pathogenic potential of two selected mutants in a left-sided, native valve IE rabbit model. Assays determining the ability of our mutant strains to produce a biofilm, bind to and aggregate platelets, and adhere to or invade endothelial cells identified sixteen genes with novel association to these phenotypes. These results suggest the presence of many uncharacterized genes involved in IE pathogenesis which may be relevant for disease progression. Two mutants identified by the above screening process -SSA_1099, encoding an RTX-like protein, and mur2, encoding a peptidoglycan hydrolase -were subsequently evaluated in vivo. Wild type (WT) S. sanguinis reliably induced cardiac vegetations, while the SSA_1099 and mur2 mutants produced either no vegetation or vegetations of small size. Splenomegaly was reduced in both mutant strains compared to WT, while pathology of other distal organs was indistinguishable. Histopathology analyses suggest the cardiac lesions and vegetations in this model resemble those observed in humans. These data indicate that SSA_1099 and mur2 encode virulence factors in S. sanguinis which are integral to pathogenesis of IE.

Global Changes in Asexual Epichloë Transcriptomes during the Early Stages, from Seed to Seedling, of Symbiotum Establishment

“…Cell wall proteins have many different roles, including defending the fungus from environmental stresses in the host environment whilst maintaining the structural integrity of the cell wall [ 73 , 79 ]. Cell wall proteins are also involved in adhesion, evident from the observation that the endophyte cell wall attaches to the host cell wall in L. perenne - E. festucae var.…”

Genome‐wide identification of Streptococcus sanguinis fitness genes in human serum and discovery of potential selective drug targets

“…To date, very few S. sanguinis genes have been confirmed as virulence factors using an animal model (Bai et al, 2019;Crump et al, 2014;Ge et al, 2008;Martini et al, 2020). We have likely identified many additional promising candidates.…”

<p>Potential Allylpyrocatechol Derivatives as Antibacterial Agent Against Oral Pathogen of<em> S. sanguinis</em> ATCC 10,556 and as Inhibitor of MurA Enzymes: in vitro and in silico Study</p>

“…The colonies of S. sanguinis can form a new environment to be localization other microorganisms, resulting in pathogenesis. 6,7 Currently, some antibiotics used as treatment stages to inhibit the bacteria, but it does not work completely, especially for pathogenic bacteria. 8 Some antibiotics make an abnormal environment that causes stress conditions to bacteria, then induce cell death.…”