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Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria

Quorum sensing (QS) is a process that regulates gene expression based on cell density. In bacteria, QS facilitates collaboration and controls a large number of pathways, including biofilm formation and virulence factor production, which lead to lower sensitivity to antibiotics and higher toxicity in...

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Detalles Bibliográficos
Autores principales: Beenker, Wouter A. G., Hoeksma, Jelmer, den Hertog, Jeroen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296082/
https://www.ncbi.nlm.nih.gov/pubmed/35865924
http://dx.doi.org/10.3389/fmicb.2022.934235
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author Beenker, Wouter A. G.
Hoeksma, Jelmer
den Hertog, Jeroen
author_facet Beenker, Wouter A. G.
Hoeksma, Jelmer
den Hertog, Jeroen
author_sort Beenker, Wouter A. G.
collection PubMed
description Quorum sensing (QS) is a process that regulates gene expression based on cell density. In bacteria, QS facilitates collaboration and controls a large number of pathways, including biofilm formation and virulence factor production, which lead to lower sensitivity to antibiotics and higher toxicity in the host, respectively. Inhibition of QS is a promising strategy to combat bacterial infections. In this study, we tested the potential of secondary metabolites from fungi to inhibit bacterial QS using a library derived from more than ten thousand different fungal strains. We used the reporter bacterium, Chromobacterium violaceum, and identified 39 fungal strains that produced QS inhibitor activity. These strains expressed two QS inhibitors that had been described before and eight QS inhibitors that had not been described before. Further testing for QS inhibitor activity against the opportunistic pathogen Pseudomonas aeruginosa led to the identification of gregatins as an interesting family of compounds with QS inhibitor activity. Although various gregatins inhibited QS in P. aeruginosa, these gregatins did not inhibit virulence factor production and biofilm formation. We conclude that gregatins inhibit some, but not all aspects of QS.
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spelling pubmed-92960822022-07-20 Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria Beenker, Wouter A. G. Hoeksma, Jelmer den Hertog, Jeroen Front Microbiol Microbiology Quorum sensing (QS) is a process that regulates gene expression based on cell density. In bacteria, QS facilitates collaboration and controls a large number of pathways, including biofilm formation and virulence factor production, which lead to lower sensitivity to antibiotics and higher toxicity in the host, respectively. Inhibition of QS is a promising strategy to combat bacterial infections. In this study, we tested the potential of secondary metabolites from fungi to inhibit bacterial QS using a library derived from more than ten thousand different fungal strains. We used the reporter bacterium, Chromobacterium violaceum, and identified 39 fungal strains that produced QS inhibitor activity. These strains expressed two QS inhibitors that had been described before and eight QS inhibitors that had not been described before. Further testing for QS inhibitor activity against the opportunistic pathogen Pseudomonas aeruginosa led to the identification of gregatins as an interesting family of compounds with QS inhibitor activity. Although various gregatins inhibited QS in P. aeruginosa, these gregatins did not inhibit virulence factor production and biofilm formation. We conclude that gregatins inhibit some, but not all aspects of QS. Frontiers Media S.A. 2022-07-05 /pmc/articles/PMC9296082/ /pubmed/35865924 http://dx.doi.org/10.3389/fmicb.2022.934235 Text en Copyright © 2022 Beenker, Hoeksma and den Hertog. 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 Microbiology
Beenker, Wouter A. G.
Hoeksma, Jelmer
den Hertog, Jeroen
Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria
title Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria
title_full Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria
title_fullStr Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria
title_full_unstemmed Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria
title_short Gregatins, a Group of Related Fungal Secondary Metabolites, Inhibit Aspects of Quorum Sensing in Gram-Negative Bacteria
title_sort gregatins, a group of related fungal secondary metabolites, inhibit aspects of quorum sensing in gram-negative bacteria
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296082/
https://www.ncbi.nlm.nih.gov/pubmed/35865924
http://dx.doi.org/10.3389/fmicb.2022.934235
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