Several bacterial pathogens possess sodC genes that encode periplasmic or membrane-associated Cu,Zn superoxide dismutases. Since professional phagocytes generate large amounts of reactive oxygen species to control the growth of invading micro-organisms, Cu,Zn superoxide dismutase might protect infectious bacteria from oxy-radical damage and facilitate their survival within the host. This idea has gained support from studies showing that sodC -null mutants of different bacteria are less virulent than their parental wild-type strains, and from the discovery that, despite apparent dispensability for growth under laboratory conditions, various pathogens (including several highly virulent Salmonella strains) possess multiple copies of sodC. Our studies indicate that Cu,Zn superoxide dismutase effectively protects bacteria from phagocytic killing, and that the role in infection of the redundant sodC genes may vary in distinct Salmonella enterica serovars. More unexpectedly, we have found that Cu,Zn superoxide dismutase also modulates bacterial survival within epithelial cells, where bacterial killing appears to be mediated by an NAD(P)H oxidase resembling the enzyme complex typical of phagocytes. Finally, a striking feature of Cu,Zn superoxide dismutases from bacterial pathogens is their apparent ability to exploit the structural versatility of the enzyme to modulate its function. In fact, several enzyme variants exhibit unique properties that may lead to the acquisition of novel specialized functions distinct from superoxide dismutation.