Lack of OxyR and KatG Results in Extreme Susceptibility of LVS to Oxidative Stress and Marked Attenuation .

is an intracellular bacterium and as such is expected to encounter a continuous attack by reactive oxygen species (ROS) in its intracellular habitat and efficiently coping with oxidative stress is therefore essential for its survival. The oxidative stress response system of is complex and includes multiple antioxidant enzymes and pathways, including the transcriptional regulator OxyR and the HO-decomposing enzyme catalase, encoded by . The latter is regulated by OxyR. A deletion of either of these genes, however, does not severely compromise the virulence of and we hypothesized that if the bacterium would be deficient of both catalase and OxyR, then the oxidative defense and virulence of would become severely hampered. To test this hypothesis, we generated a double deletion mutant, ΔΔ, of LVS and compared its phenotype to the parental LVS strain and the corresponding single deletion mutants. In accordance with the hypothesis, ΔΔ was distinctly more susceptible than Δ and Δ to HO, ONOO, and [Formula: see text], moreover, it hardly grew in mouse-derived BMDM or in mice, whereas Δ and Δ grew as well as LVS in BMDM and exhibited only slight attenuation in mice. Altogether, the results demonstrate the importance of catalase and OxyR for a robust oxidative stress defense system and that they act cooperatively. The lack of both functions render severely crippled to handle oxidative stress and also much attenuated for intracellular growth and virulence.