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Glucocorticoids increase tissue cell protection against pore-forming toxins from pathogenic bacteria

THOMAS ORMSBY, Sian-eleri Owens Orcid Logo, Matthew Turner Orcid Logo, James Cronin Orcid Logo, John J. Bromfield Orcid Logo, Martin Sheldon Orcid Logo

Communications Biology, Volume: 6, Issue: 1, Pages: 1 - 15

Swansea University Authors: THOMAS ORMSBY, Sian-eleri Owens Orcid Logo, Matthew Turner Orcid Logo, James Cronin Orcid Logo, Martin Sheldon Orcid Logo

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Abstract

Many species of pathogenic bacteria damage tissue cells by secreting toxins that form pores in plasma membranes. Here we show that glucocorticoids increase the intrinsic protection of tissue cells against pore-forming toxins. Dexamethasone protected several cell types against the cholesterol-depende...

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Published in: Communications Biology
ISSN: 2399-3642
Published: Springer Science and Business Media LLC 2023
Online Access: Check full text

URI: https://cronfa.swan.ac.uk/Record/cronfa62675
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Abstract: Many species of pathogenic bacteria damage tissue cells by secreting toxins that form pores in plasma membranes. Here we show that glucocorticoids increase the intrinsic protection of tissue cells against pore-forming toxins. Dexamethasone protected several cell types against the cholesterol-dependent cytolysin, pyolysin, from Trueperella pyogenes. Dexamethasone treatment reduced pyolysin-induced leakage of potassium and lactate dehydrogenase, limited actin cytoskeleton alterations, reduced plasma membrane blebbing, and prevented cytolysis. Hydrocortisone and fluticasone also protected against pyolysin-induced cell damage. Furthermore, dexamethasone protected HeLa and A549 cells against the pore-forming toxins streptolysin O from Streptococcus pyogenes, and alpha-hemolysin from Staphylococcus aureus. Dexamethasone cytoprotection was not associated with changes in cellular cholesterol or activating mitogen-activated protein kinase (MAPK) cell stress responses. However, cytoprotection was dependent on the glucocorticoid receptor and 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR). Collectively, our findings imply that glucocorticoids could be exploited to limit tissue damage caused by pathogens secreting pore-forming toxins.
Item Description: Data availability:All data generated or analyzed during this study, and uncropped Western blots, are included in this published article and its supplementary information files. The datasets generated and analyzed during the current study are available in Supplementary Data 1. All other data are available from the corresponding author on reasonable request.
College: Faculty of Medicine, Health and Life Sciences
Funders: This study was supported by the Biotechnology and Biological Sciences Research Council (BB/K006592/1) and the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (R01HD084316).
Issue: 1
Start Page: 1
End Page: 15