Streptococcus sanguinis colonizes teeth and is an important cause of
infective endocarditis. Our prior work showed that the
lipoprotein SsaB is critical for S. sanguinis virulence for
endocarditis and belongs to the LraI family of conserved
metal transporters. In this study, we demonstrated that an
ssaB mutant accumulates less
manganese and
iron than its parent. A mutant lacking the
manganese-dependent
superoxide dismutase, SodA, was significantly less virulent than wild-type in a rabbit model of
endocarditis, but significantly more virulent than the
ssaB mutant. Neither the
ssaB nor the sodA mutation affected sensitivity to phagocytic killing or efficiency of heart valve colonization. Animal virulence results for all strains could be reproduced by growing bacteria in serum under physiological levels of O(2). SodA activity was reduced, but not eliminated in the
ssaB mutant in serum and in rabbits. Growth of the
ssaB mutant in serum was restored upon addition of Mn(2+) or removal of O(2).
Antioxidant supplementation experiments suggested that
superoxide and
hydroxyl radicals were together responsible for the
ssaB mutant's growth defect. We conclude that
manganese accumulation mediated by the
SsaB transport system imparts virulence by enabling cell growth in
oxygen through SodA-dependent and independent mechanisms.