Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis.

ABSTRACT: Staphylococcus aureus small colony variants (SCVs) are frequently associated with chronic infection, yet they lack expression of many virulence determinants associated with the pathogenicity of wild-type strains. We found that both wild-type S. aureus and a ΔhemB SCV prototype potently activate glycolysis in host cells. Glycolysis and the generation of mitochondrial reactive oxygen species were sufficient to induce necroptosis, a caspase-independent mechanism of host cell death that failed to eradicate S. aureus and instead promoted ΔhemB SCV pathogenicity. To support ongoing glycolytic activity, the ΔhemB SCV induced over a 100-fold increase in the expression of fumC, which encodes an enzyme that catalyses the degradatin of fumarate, an inhibitor of glycolysis. Consistent with fumC-depend

SUBMITTER: Wong Fok Lung T 

PROVIDER: S-EPMC10184863 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature