Oxidative stress tolerance is manganese (Mn2+) regulated in Streptococcus gordonii

The Sca permease in the oral bacterium Streptococcus gordonii is a member of a family of ATP-binding cassette (ABC)-type transporters for manganese (Mn(2+)) and related cations that are associated with streptococcal virulence in a number of infection models. Since Mn(2+) has a protective function against oxidative damage in a variety of bacteria, we have investigated the role of Sca permease in oxidative stress tolerance in Streptococcus gordonii. A single Mn(2+)-dependent superoxide dismutase (SOD), encoded by sodA, is expressed by S. gordonii and was >10-fold up-regulated under oxidative stress conditions. Inactivation of sodA resulted in increased susceptibility of S. gordonii cells to growth inhibition by dioxygen (O(2)), and to killing by paraquat (a superoxide anion generator) and by hydrogen peroxide (H(2)O(2)). Expression of thiol peroxidase, encoded by the tpx gene located immediately downstream of the scaCBA operon, was also up-regulated under oxidative conditions. Inactivation of tpx led to increased susceptibility of cells to H(2)O(2), but not to O(2) or paraquat. In low-Mn(2+) medium (0.01 micro M Mn(2+)) sodA and tpx genes were transcriptionally down-regulated, SOD activity was reduced and cells were more sensitive to growth inhibition by O(2). A Sca permease-deficient (scaC) mutant showed further reduced SOD activity and hypersensitivity to O(2) in medium containing <0.1 micro M Mn(2+). These results demonstrate that the Sca (Mn(2+)) permease in S. gordonii is essential for protection against oxidative stress.