Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/22078
Title: Staphylococcus aureus small colony variants impair host immunity by activating host cell glycolysis and inducing necroptosis.
Austin Authors: Wong Fok Lung, Tania;Monk, Ian R;Acker, Karen P;Mu, Andre;Wang, Nancy;Riquelme, Sebastián A;Pires, Silvia;Noguera, Loreani P;Dach, Felix;Gabryszewski, Stanislaw J;Howden, Benjamin P ;Prince, Alice
Affiliation: Department of Pediatrics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Microbiological Diagnostic Unit Public Health Laboratory, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Department of Pediatrics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
Department of Infectious Diseases, Austin Health, Heidelberg, Victoria, Australia
Department of Pediatrics, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA
Issue Date: Jan-2020
metadata.dc.date: 2019-11-04
Publication information: Nature microbiology 2019; 5(1): 141-153
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-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.
URI: http://ahro.austin.org.au/austinjspui/handle/1/22078
DOI: 10.1038/s41564-019-0597-0
ORCID: 0000-0002-9318-9572
0000-0001-6982-8074
0000-0001-6559-5517
0000-0002-0853-9743
0000-0001-7623-1858
0000-0003-3478-5769
0000-0002-6373-5376
0000-0003-0237-1473
0000-0002-7399-9295
PubMed URL: 31686028
Type: Journal Article
Appears in Collections:Journal articles

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