A novel infective endocarditis virulence factor related to multiple functions for bacterial survival in blood was discovered in Streptococcus sanguinis

We identified the role of a conserved hypothetical protein (SSA_0451) in S. sanguinis that is involved in the virulence of infective endocarditis. An in vitro whole blood killing assay and rabbit endocarditis model studies revealed that the SSA_0451 mutant ({Delta}SSA_0451) was significantly less virulent than the wild-type (SK36) and its complementation mutant ({Delta}SSA_0451C). The mechanism underlying the SSA_0451 mutants reduced virulence in infective endocarditis was evidentially linked to oxidative stress and environmental stress. The genes related to the survival of S. sanguinis in an oxidative stress environment were downregulated in {Delta}SSA_0451, which affected its survival in blood. Our findings suggest that SSA_0451 is a novel IE virulence factor and a new target for drug discovery against IE. Author summaryThis study focused on SSA_0451, a conserved hypothetical protein in S. sanguinis, to explore its potential role as a virulence factor. Through in vitro whole blood killing assays and rabbit IE models, it was found that the SSA_0451 mutant exhibited reduced virulence compared to the wild-type and a complemented mutant. The study linked the mutants diminished virulence in IE to heightened susceptibility to oxidative and environmental stresses, supported by downregulation of genes crucial for oxidative stress survival in S. sanguinis. These findings identify SSA_0451 as a novel virulence factor in IE and propose it as a promising target for future drug development against this condition.