Contribution of metal transporters of the ABC, ZIP, and NRAMP families to manganese uptake and infective endocarditis virulence in Streptococcus sanguinis

Streptococcus sanguinis is an important cause of infective endocarditis. In strain SK36, the ABC-family manganese transporter, SsaACB, is essential for virulence. We have now identified a ZIP-family protein, TmpA, as a secondary manganese transporter. A tmpA mutant had no phenotype, but a Δ ssaACB Δ tmpA mutant was far more attenuated for serum growth and somewhat more attenuated for virulence in a rabbit model than its Δ ssaACB parent. The growth of both mutants was restored by supplemental manganese, but the Δ ssaACB Δ tmpA mutant required twenty-fold more and accumulated less. Although ZIP-family proteins are known for zinc and iron transport, TmpA-mediated transport of either metal was minimal. In contrast to ssaACB and tmpA , which appear ubiquitous in S. sanguinis , a mntH gene encoding an NRAMP-family transporter has been identified in relatively few strains, including VMC66. As in SK36, deletion of ssaACB greatly diminished VMC66 endocarditis virulence and serum growth, and deletion of tmpA from this mutant diminished virulence further. Virulence was not significantly altered by deletion of mntH from either VMC66 or its Δ ssaACB mutant. This and the accompanying paper together suggest that SsaACB is of primary importance for endocarditis virulence while secondary transporters TmpA and MntH contribute to growth under differing conditions. ### Competing Interest Statement The authors have declared no competing interest.