The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept

ABSTRACT Antivirulence drugs disarm rather than kill pathogens and are thought to alleviate the problem of resistance, although there is no evidence to support this notion. Quorum sensing (QS) often controls cooperative virulence factor production and is therefore an attractive antivirulence target,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Brett Mellbye, Martin Schuster
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5401bcbe5c3441c08db1b61ea2a0548e
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5401bcbe5c3441c08db1b61ea2a0548e
record_format	dspace
spelling	oai:doaj.org-article:5401bcbe5c3441c08db1b61ea2a0548e2021-11-15T15:38:58ZThe Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept10.1128/mBio.00131-112150-7511https://doaj.org/article/5401bcbe5c3441c08db1b61ea2a0548e2011-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00131-11https://doaj.org/toc/2150-7511ABSTRACT Antivirulence drugs disarm rather than kill pathogens and are thought to alleviate the problem of resistance, although there is no evidence to support this notion. Quorum sensing (QS) often controls cooperative virulence factor production and is therefore an attractive antivirulence target, for which inhibitors (QSI) have been developed. We designed a proof-of-principle experiment to investigate the impact of bacterial social interactions on the evolution of QSI resistance. We cocultured Pseudomonas aeruginosa QS-deficient mutants with small proportions of the QS-proficient wild type, which in the absence of QSI mimic QSI-sensitive and -resistant variants, respectively. We employed two different QS-dependent nutrients that are degraded by extracellular (public) and cell-associated (private) enzymes. QS mutants (QSI-sensitive mimics) behaved as social cheaters that delayed population growth and prevented enrichment of wild-type cooperators (QSI-resistant mimics) only when nutrient acquisition was public, suggesting that QSI resistance would not spread. This highlights the potential for antivirulence strategies that target cooperative behaviors and provides a conceptual framework for future studies.Brett MellbyeMartin SchusterAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 5 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Brett Mellbye Martin Schuster The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept
description	ABSTRACT Antivirulence drugs disarm rather than kill pathogens and are thought to alleviate the problem of resistance, although there is no evidence to support this notion. Quorum sensing (QS) often controls cooperative virulence factor production and is therefore an attractive antivirulence target, for which inhibitors (QSI) have been developed. We designed a proof-of-principle experiment to investigate the impact of bacterial social interactions on the evolution of QSI resistance. We cocultured Pseudomonas aeruginosa QS-deficient mutants with small proportions of the QS-proficient wild type, which in the absence of QSI mimic QSI-sensitive and -resistant variants, respectively. We employed two different QS-dependent nutrients that are degraded by extracellular (public) and cell-associated (private) enzymes. QS mutants (QSI-sensitive mimics) behaved as social cheaters that delayed population growth and prevented enrichment of wild-type cooperators (QSI-resistant mimics) only when nutrient acquisition was public, suggesting that QSI resistance would not spread. This highlights the potential for antivirulence strategies that target cooperative behaviors and provides a conceptual framework for future studies.
format	article
author	Brett Mellbye Martin Schuster
author_facet	Brett Mellbye Martin Schuster
author_sort	Brett Mellbye
title	The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept
title_short	The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept
title_full	The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept
title_fullStr	The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept
title_full_unstemmed	The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept
title_sort	sociomicrobiology of antivirulence drug resistance: a proof of concept
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/5401bcbe5c3441c08db1b61ea2a0548e
work_keys_str_mv	AT brettmellbye thesociomicrobiologyofantivirulencedrugresistanceaproofofconcept AT martinschuster thesociomicrobiologyofantivirulencedrugresistanceaproofofconcept AT brettmellbye sociomicrobiologyofantivirulencedrugresistanceaproofofconcept AT martinschuster sociomicrobiologyofantivirulencedrugresistanceaproofofconcept
_version_	1718427825529159680

The Sociomicrobiology of Antivirulence Drug Resistance: a Proof of Concept

Ejemplares similares