Corynebacterium pseudotuberculosis phospholipase D targets mitochondrial sphingomyelin and induces NLRP3-GSDMD axis-mediated pyroptosis in macrophages to promote infection.

ABSTRACT: Infection by Corynebacterium pseudotuberculosis (Cp), a facultative intracellular bacterium, causes mainly purulent inflammation and chronic granulomas in animals and humans. Pyroptosis is a proinflammatory form of programmed cell death that is important in response to pathogen infection. The role of pyroptosis in Cp infection and the related mechanisms are still unclear. Here, we reveal that Cp infection induces pyroptosis in macrophages. The inhibition of pyroptosis by disulfiram (DSF) or dimethyl fumarate (DMF) decreases the pathogenicity of Cp in mice and prevents the escape of this pathogen from infected macrophages. In contrast, LPS treatment achieves the opposite results in mice and macrophages infected with Cp. In addition, we revealed that phospholipase D (PLD) is a key virulence

SUBMITTER: Li X 

PROVIDER: S-EPMC12533471 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature