PERIPLASMIC SUPEROXIDE-DISMUTASE IN MENINGOCOCCAL PATHOGENICITY

Meningococcal sodC encodes periplasmic copper and zinc-cofactored supe roxide dismutase (Cu,Zn SOD) which catalyzes the conversion of the sup eroxide radical anion to hydrogen peroxide, preventing a sequence of r eactions leading to production of toxic hydroxyl free radicals, From i ts periplasmic location, Cu,Zn SOD was inferred to acquire its substra te from outside the bacterial cell and was speculated to play a role i n preserving meningococci from the action of microbicidal oxygen free radicals produced in the context of host defense, A sodC mutant was co nstructed by allelic exchange and was used to investigate the role of Cu,Zn SOD in pathogenicity. Wild-type and mutant meningococci grew at comparable rates and survived equally long in aerobic liquid culture, The mutant showed no increased sensitivity to paraquat, which generate s superoxide within the cytosol, but was approximately 1,000-fold more sensitive to the toxicity of superoxide generated in solution by the xanthine/xanthine oxidase system, These data support a role for mening ococcal Cu,Zn SOD in protection against exogenous superoxide, In exper iments to translate this into a role in pathogenicity, wild-type and m utant organisms were used in an intraperitoneal mouse infection model, The sodC mutant was significantly less virulent, We conclude that per iplasmic Cu,Zn SOD contributes to the virulence of Neisseria meningiti dis, most likely by reducing the effectiveness of toxic oxygen host de fenses.