Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability

ABSTRACT Quorum sensing (QS) is a microbial cell-cell communication system that regulates gene expression in response to population density to coordinate collective behaviors. Yet, the role of QS in resolving the stresses caused by the accumulation of toxic metabolic by-products at high cell density...

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Autores principales:	Lisa A. Hawver, Jennifer M. Giulietti, James D. Baleja, Wai-Leung Ng
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ae97de37ac5347559491c6428f75da83
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spelling	oai:doaj.org-article:ae97de37ac5347559491c6428f75da832021-11-15T15:50:16ZQuorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability10.1128/mBio.01863-162150-7511https://doaj.org/article/ae97de37ac5347559491c6428f75da832016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01863-16https://doaj.org/toc/2150-7511ABSTRACT Quorum sensing (QS) is a microbial cell-cell communication system that regulates gene expression in response to population density to coordinate collective behaviors. Yet, the role of QS in resolving the stresses caused by the accumulation of toxic metabolic by-products at high cell density is not well defined. In response to cell density, QS could be involved in reprogramming of the metabolic network to maintain population stability. Using unbiased metabolomics, we discovered that Vibrio cholerae mutants genetically locked in a low cell density (LCD) QS state are unable to alter the pyruvate flux to convert fermentable carbon sources into neutral acetoin and 2,3-butanediol molecules to offset organic acid production. As a consequence, LCD-locked QS mutants rapidly lose viability when grown with fermentable carbon sources. This key metabolic switch relies on the QS-regulated small RNAs Qrr1-4 but is independent of known QS regulators AphA and HapR. Qrr1-4 dictate pyruvate flux by translational repression of the enzyme AlsS, which carries out the first step in acetoin and 2,3-butanediol biosynthesis. Consistent with the idea that QS facilitates the expression of a common trait in the population, AlsS needs to be expressed cooperatively in a group of cells. Heterogeneous populations with high percentages of cells not expressing AlsS are unstable. All of the cells, regardless of their respective QS states, succumb to stresses caused by toxic by-product accumulation. Our results indicate that the ability of the bacteria to cooperatively control metabolic flux through QS is critical in maintaining a sustainable environment and overall population stability. IMPORTANCE Our work reveals a novel role for Vibrio cholerae quorum sensing (QS) in relieving the stresses caused by toxic metabolite accumulation when the population becomes crowded through metabolic reprogramming. QS enables V. cholerae switching from a low cell density energy-generating metabolism that is beneficial to individuals at the expense of the environment to a high cell density mode that preserves environmental habitability by sacrificing individual fitness. This cooperative switch provides a stable environment as the common good in maintaining the stability of the community. However, the common good can be exploited by uncooperative mutants that pollute the environment, causing population collapse. Our findings provide insights into the metabolic stress response of a major human pathogen, with implications for our understanding of microbial social biology and cooperation from an ecological and evolutionary perspective.Lisa A. HawverJennifer M. GiuliettiJames D. BalejaWai-Leung NgAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Lisa A. Hawver Jennifer M. Giulietti James D. Baleja Wai-Leung Ng Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability
description	ABSTRACT Quorum sensing (QS) is a microbial cell-cell communication system that regulates gene expression in response to population density to coordinate collective behaviors. Yet, the role of QS in resolving the stresses caused by the accumulation of toxic metabolic by-products at high cell density is not well defined. In response to cell density, QS could be involved in reprogramming of the metabolic network to maintain population stability. Using unbiased metabolomics, we discovered that Vibrio cholerae mutants genetically locked in a low cell density (LCD) QS state are unable to alter the pyruvate flux to convert fermentable carbon sources into neutral acetoin and 2,3-butanediol molecules to offset organic acid production. As a consequence, LCD-locked QS mutants rapidly lose viability when grown with fermentable carbon sources. This key metabolic switch relies on the QS-regulated small RNAs Qrr1-4 but is independent of known QS regulators AphA and HapR. Qrr1-4 dictate pyruvate flux by translational repression of the enzyme AlsS, which carries out the first step in acetoin and 2,3-butanediol biosynthesis. Consistent with the idea that QS facilitates the expression of a common trait in the population, AlsS needs to be expressed cooperatively in a group of cells. Heterogeneous populations with high percentages of cells not expressing AlsS are unstable. All of the cells, regardless of their respective QS states, succumb to stresses caused by toxic by-product accumulation. Our results indicate that the ability of the bacteria to cooperatively control metabolic flux through QS is critical in maintaining a sustainable environment and overall population stability. IMPORTANCE Our work reveals a novel role for Vibrio cholerae quorum sensing (QS) in relieving the stresses caused by toxic metabolite accumulation when the population becomes crowded through metabolic reprogramming. QS enables V. cholerae switching from a low cell density energy-generating metabolism that is beneficial to individuals at the expense of the environment to a high cell density mode that preserves environmental habitability by sacrificing individual fitness. This cooperative switch provides a stable environment as the common good in maintaining the stability of the community. However, the common good can be exploited by uncooperative mutants that pollute the environment, causing population collapse. Our findings provide insights into the metabolic stress response of a major human pathogen, with implications for our understanding of microbial social biology and cooperation from an ecological and evolutionary perspective.
format	article
author	Lisa A. Hawver Jennifer M. Giulietti James D. Baleja Wai-Leung Ng
author_facet	Lisa A. Hawver Jennifer M. Giulietti James D. Baleja Wai-Leung Ng
author_sort	Lisa A. Hawver
title	Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability
title_short	Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability
title_full	Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability
title_fullStr	Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability
title_full_unstemmed	Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability
title_sort	quorum sensing coordinates cooperative expression of pyruvate metabolism genes to maintain a sustainable environment for population stability
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/ae97de37ac5347559491c6428f75da83
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_version_	1718427478297411584

Quorum Sensing Coordinates Cooperative Expression of Pyruvate Metabolism Genes To Maintain a Sustainable Environment for Population Stability

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