During infection, Staphylococcus aureus and other pathogens must obtain all of their nutrients from the host. To combat invaders, vertebrates take advantage of this fact and restrict the availability of essential nutrients such as manganese and zinc. Currently, the adaptations that enable pathogens to overcome host-imposed manganese and zinc starvation remain largely unknown. Utilizing the manganese and zinc binding immune effector calprotectin and mice with defects in metal sequestration, we have begun to elucidate how S. aureus overcomes this defense known as nutritional immunity. Differing from most staphylococci, S. aureus possesses two superoxide dismutases. Our investigations have revealed that acquisition of the second superoxide dismutase, SodM, enables S. aureus to overcome nutritional immunity and cause infection. Differing from SodA, which all staphylococci have, our analysis revealed that SodM is capable of functioning with either manganese or iron. The cambialistic nature of SodM enables S. aureus to retain an antioxidant defense in the presence of calprotectin and better resist oxidative stress. While biochemical studies have previously suggested the existence of superoxide dismutases capable of using iron or manganese, the biological importance of cambialism has remained controversial. Cumulatively, these studies provide a mechanistic rationale for the acquisition of a second superoxide dismutase by S. aureus and demonstrate an important contribution of cambialistic superoxide dismutases to bacterial pathogenesis. Furthermore, they also suggest a new mechanism for resisting manganese starvation, namely populating manganese-utilizing enzymes with iron.