SodC is responsible for oxidative stress resistance and pathogenicity of Corynebacterium pseudotuberculosis, and the sodC-deleted C. pseudotuberculosis vaccine provides immunity in mice

Abstract

Corynebacterium pseudotuberculosis causes chronic inflammatory infectious diseases in animals and humans. Resistance to adverse environments, including oxidative stress, is required for the survival and pathogenicity of C. pseudotuberculosis. Superoxide dismutase (SOD) is a key enzyme to resist oxidative stress. However, the role of SODs in C. pseudotuberculosis has not been reported. In this study, we addressed this question using C. pseudotuberculosis XH02, sodA deleted (XH02ΔsodA), and sodC deleted (XH02ΔsodC) strains. We found that sodA or sodC deletion reduced the pathogenicity of C. pseudotuberculosis in mice, decreased bacterial loads and histopathological lesions in the infected organs. In addition, the deletion of sodC in C. pseudotuberculosis significantly decreased IL-1β secretion, lactate dehydrogenase (LDH) release, and propidium iodide (PI) uptake of the infected J774A.1 macrophages. Furthermore, sodC deletion weakened the biofilm formation ability of C. pseudotuberculosis, reduced the survival of C. pseudotuberculosis within macrophages, and decreased the ability of C. pseudotuberculosis to resist oxidative stress. We observed that mutations at H94E, H96E, H111A, and H166E reduced the enzyme activity of SodC and reduced the resistance to oxidative stress. Finally, XH02ΔsodC immunization in mice increased specific IgG level and CD4⁺/CD8⁺ T cells ratio, and protected mice against C. pseudotuberculosis challenge. Thus, this study confirmed that SodC is an important virulence-related factor of C. pseudotuberculosis, and plays crucial roles in oxidative stress resistance. XH02ΔsodC can be used as a potential candidate attenuated vaccine to prevent and control C. pseudotuberculosis infection.