Pathogenic leptospires are responsible for the zoonotic disease leptospirosis. The clinical manifestations of this infection range from a febrile state to a severe life-threatening form characterized by multiple organ hemorrhages. More than one million cases of leptospirosis are currently reported annually in the word, with 10% of mortality. Leptospira penetrate hosts and rapidly disseminate to target organs (including kidney, liver, lungs) throughout the bloodstream. During infection, Leptospira are confronted with dramatic adverse environmental changes such as deadly reactive oxygen species (ROS). We used proteomic analyses to identify the factors that constitute the adaptive response to superoxide stress in the pathogenic model Leptospira interrogans.