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Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa

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 pers...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494450/
https://www.ncbi.nlm.nih.gov/pubmed/34631600
http://dx.doi.org/10.3389/fcimb.2021.718213
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author 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.
author_facet 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.
author_sort Fraser-Pitt, Douglas J.
collection PubMed
description 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.
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spelling pubmed-84944502021-10-07 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. Front Cell Infect Microbiol Cellular and Infection Microbiology 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. Frontiers Media S.A. 2021-09-22 /pmc/articles/PMC8494450/ /pubmed/34631600 http://dx.doi.org/10.3389/fcimb.2021.718213 Text en Copyright © 2021 Fraser-Pitt, Dolan, Toledo-Aparicio, Hunt, Smith, Lacy-Roberts, Nupe Hewage, Stoyanova, Manson, McClean, Inglis, Mercer and O’Neil https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
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.
Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa
title Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa
title_full Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa
title_fullStr Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa
title_full_unstemmed Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa
title_short Cysteamine Inhibits Glycine Utilisation and Disrupts Virulence in Pseudomonas aeruginosa
title_sort cysteamine inhibits glycine utilisation and disrupts virulence in pseudomonas aeruginosa
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494450/
https://www.ncbi.nlm.nih.gov/pubmed/34631600
http://dx.doi.org/10.3389/fcimb.2021.718213
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