坏死性下垂
糖酵解
金黄色葡萄球菌
微生物学
生物
毒力
免疫
程序性细胞死亡
寄主(生物学)
免疫系统
细菌
基因
免疫学
酶
细胞凋亡
遗传学
生物化学
作者
Tania Wong Fok Lung,Ian R. Monk,Karen P. Acker,Andre Mu,Nancy Wang,Sebastián Riquelme-Barrios,Sílvia Pires,Loreani P. Noguera,Felix Dach,Stanislaw J. Gabryszewski,Benjamin P. Howden,Alice Prince
出处
期刊:Nature microbiology
日期:2019-11-04
卷期号:5 (1): 141-153
被引量:77
标识
DOI:10.1038/s41564-019-0597-0
摘要
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-dependent depletion of local fumarate, the ΔhemB SCV failed to elicit trained immunity and protection from a secondary infectious challenge in the skin. The reliance of the S. aureus SCV population on glycolysis accounts for much of its role in the pathogenesis of S. aureus skin infection. Small colony variants of Staphylococcus aureus induce glycolysis and necroptosis in host cells, which impairs trained immunity and host protection from subsequent S. aureus infection.
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