10.3389/fcimb.2021.718213
Cysteamine inhibits glycine utilisation and disrupts virulence in pseudomonas aeruginosa. [Dataset]
Fraser-Pitt, Douglas J.
Douglas J.
Fraser-Pitt
Dolan, Stephen K.
Stephen K.
Dolan
Toledo-Aparicio, David
David
Toledo-Aparicio
Hunt, Jessica G.
Jessica G.
Hunt
Smith, Daniel W.
Daniel W.
Smith
Lacy-Roberts, Niamh
Niamh
Lacy-Roberts
Nupe Hewage, Piumi Sara
Piumi Sara
Nupe Hewage
Stoyanova, Teodora N.
Teodora N.
Stoyanova
Manson, Erin
Erin
Manson
McClean, Kevin
Kevin
McClean
Inglis, Neil F.
Neil F.
Inglis
Mercer, Derry K.
Derry K.
Mercer
O'Neil, Deborah A.
Deborah A.
O'Neil
Unknown
2021
Virulence; Biofilm; Pseudomonas aeruginosa; Novel therapeutic; Glycine cleavage complex
2021-07-07
Dataset
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 reported activity blocking the glycine cleavage system in human cells. Despite the inhibition of glycine metabolism, cysteamine inhibits hydrogen cyanide (HCN) production by P. aeruginosa, implicating interference in the regulation of virulence. Cysteamine impaired chemotaxis and reductions in pyocyanin and exopolysaccharide production in cysteamine-treated P. aeruginosa and reduced toxicity of secreted factors in a Galleria mellonella model. Thus, cysteamine has additional potent anti-virulence properties targeting P. aeruginosa, further supporting its therapeutic potential in CF and other infections.