While Streptococcus sanguinis plays a beneficial role in the oral cavity as a competitor of Streptococcus mutans and Streptococcus sobrinus , the bacteria that produce dental caries, it can cause deadly infective endocarditis if given the opportunity to colonize the vegetations that form over damaged endocardial tissue. Pre-existing heart conditions, surgery, and intravenous drug use predispose individuals to endocarditis. S. sanguinis growth and consequential virulence is significantly impeded

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... by restriction to manganese. This is due to the resulting overwhelming oxidative stress and formation of reactive oxygen species which damage DNA and other cellular components. Manganese is essential for S. sanguinis proteins involved in DNA synthesis and is predicted to play other important roles. This study investigates the importance of the previously identified manganese transporter SsaACB, of the Lral family of conserved metal transporters, in combination with other proteins, such as ComCDE, SSA_0872, LguL, SSA_1625, and NrdD, for strain survival in vitro . These proteins of interest were selected because notable accumulation or reduction of associated metabolites in a metabolomic study suggested causation for the loss of virulence of the ssaACB knockout strain in vivo . A serum growth study of strains with single and double knockout mutations incubated at physiological conditions was conducted and the results were further supported by observation of fermenter culture growth after chelation of free manganese ions to exacerbate the effects of manganese starvation. This study identified combinations of proteins which are not essential for manganese-dependent S. sanguinis growth. 1