Journal article

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

Tania Wong Fok Lung, Ian R Monk, Karen P Acker, Andre Mu, Nancy Wang, Sebastian A Riquelme, Silvia Pires, Loreani P Noguera, Felix Dach, Stanislaw J Gabryszewski, Benjamin P Howden, Alice Prince

NATURE MICROBIOLOGY | NATURE PUBLISHING GROUP | Published : 2020

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 enzym..

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Grants

Awarded by NIH


Awarded by NHMRC grant (Australia)


Funding Acknowledgements

We thank I. Lewis (University of Calgary), R. Groves (University of Calgary) and D. P. De Souza (Metabolomics Australia) for their support with the metabolomics studies and V. J. Torres (New York University School of Medicine) for his gift of antibodies against staphylococci toxins. This work was supported by NIH grant R01AI103854 to A.P., NIH grant S10RR027050 to the Columbia Center for Translational Immunology Flow Cytometry Core and NHMRC grant (Australia) APP1066791 to B.P.H.