Skip to main content

Research Repository

Advanced Search

Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa

Fraser-Pitt, Douglas J.; Dolan, Stephen K.; Toledo-Aparicio, David; Hunt, Jessica G.; Smith, Daniel W.; Lacy-Roberts, Niamh; Nupe Hewage, Piumi Sara; Stoyanova, Teodora N.; Manson, Erin; McClean, Kevin; Inglis, Neil F.; Mercer, Derry K.; O’Neil, Deborah A.

Authors

Stephen K. Dolan

David Toledo-Aparicio

Jessica G. Hunt

Daniel W. Smith

Niamh Lacy-Roberts

Piumi Sara Nupe Hewage

Teodora N. Stoyanova

Erin Manson

Kevin McClean

Neil F. Inglis

Derry K. Mercer

Deborah A. O’Neil



Abstract

Pseudomonas aeruginosa is a major opportunistic human pathogen which employs a myriad of virulence factors. In people with cystic fibrosis (CF) P. aeruginosa frequently colonises the lungs and becomes a chronic infection that evolves to become less virulent over time, but often adapts to favour persistence in the host with alginate-producing mucoid, slow-growing, and antibiotic resistant phenotypes emerging. Cysteamine is an endogenous aminothiol which has been shown to prevent biofilm formation, reduce phenazine production, and potentiate antibiotic activity against P. aeruginosa, and has been investigated in clinical trials as an adjunct therapy for pulmonary exacerbations of CF. Here we demonstrate (for the first time in a prokaryote) that cysteamine prevents glycine utilisation by P. aeruginosa in common with previously reported activity blocking the glycine cleavage system in human cells. Despite the clear inhibition of glycine metabolism, cysteamine also inhibits hydrogen cyanide (HCN) production by P. aeruginosa, suggesting a direct interference in the regulation of virulence factor synthesis. Cysteamine impaired chemotaxis, lowered pyocyanin, pyoverdine and exopolysaccharide production, and reduced the toxicity of P. aeruginosa secreted factors in a Galleria mellonella infection model. Thus, cysteamine has additional potent anti-virulence properties targeting P. aeruginosa, further supporting its therapeutic potential in CF and other infections

Citation

Fraser-Pitt, D. J., Dolan, S. K., Toledo-Aparicio, D., Hunt, J. G., Smith, D. W., Lacy-Roberts, N., …O’Neil, D. A. (in press). Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa. Frontiers in Cellular and Infection Microbiology, 11, https://doi.org/10.3389/fcimb.2021.718213

Journal Article Type Article
Acceptance Date Aug 11, 2021
Online Publication Date Sep 22, 2021
Deposit Date Dec 10, 2024
Journal Frontiers in Cellular and Infection Microbiology
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 11
DOI https://doi.org/10.3389/fcimb.2021.718213
Public URL https://keele-repository.worktribe.com/output/1013931


You might also like



Downloadable Citations