A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase

ABSTRACT Escherichia coli populations undergo repeated replacement of parental genotypes with fitter variants deep in stationary phase. We isolated one such variant, which emerged after 3 weeks of maintaining an E. coli K-12 population in stationary phase. This variant displayed a small colony pheno...

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Autores principales:	Pabitra Nandy, Savita Chib, Aswin Seshasayee
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	E. coli GASP RNA polymerase stationary phase stress response Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e46bc44df63349be983049252c95953f
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spelling	oai:doaj.org-article:e46bc44df63349be983049252c95953f2021-11-15T15:29:16ZA Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase10.1128/mSphere.00092-202379-5042https://doaj.org/article/e46bc44df63349be983049252c95953f2020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00092-20https://doaj.org/toc/2379-5042ABSTRACT Escherichia coli populations undergo repeated replacement of parental genotypes with fitter variants deep in stationary phase. We isolated one such variant, which emerged after 3 weeks of maintaining an E. coli K-12 population in stationary phase. This variant displayed a small colony phenotype and slow growth and was able to outcompete its ancestor over a narrow time window in stationary phase. The variant also shows tolerance to beta-lactam antibiotics, though not previously exposed to the antibiotic. We show that an RpoC(A494V) mutation confers the slow growth and small colony phenotype on this variant. The ability of this mutation to confer a growth advantage in stationary phase depends on the availability of the stationary-phase sigma factor σS. The RpoC(A494V) mutation upregulates the σS regulon. As shown over 20 years ago, early in prolonged stationary phase, σS attenuation, but not complete loss of activity, confers a fitness advantage. Our study shows that later mutations enhance σS activity, either by mutating the gene for σS directly or via mutations such as RpoC(A494V). The balance between the activities of the housekeeping major sigma factor and σS sets up a trade-off between growth and stress tolerance, which is tuned repeatedly during prolonged stationary phase. IMPORTANCE An important general mechanism of a bacterium’s adaptation to its environment involves adjusting the balance between growing fast and tolerating stresses. One paradigm where this plays out is in prolonged stationary phase: early studies showed that attenuation, but not complete elimination, of the general stress response enables early adaptation of the bacterium E. coli to the conditions established about 10 days into stationary phase. We show here that this balance is not static and that it is tilted back in favor of the general stress response about 2 weeks later. This can be established by direct mutations in the master regulator of the general stress response or by mutations in the core RNA polymerase enzyme itself. These conditions can support the development of antibiotic tolerance although the bacterium is not exposed to the antibiotic. Further exploration of the growth-stress balance over the course of stationary phase will necessarily require a deeper understanding of the events in the extracellular milieu.Pabitra NandySavita ChibAswin SeshasayeeAmerican Society for MicrobiologyarticleE. coliGASPRNA polymerasestationary phasestress responseMicrobiologyQR1-502ENmSphere, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	E. coli GASP RNA polymerase stationary phase stress response Microbiology QR1-502
spellingShingle	E. coli GASP RNA polymerase stationary phase stress response Microbiology QR1-502 Pabitra Nandy Savita Chib Aswin Seshasayee A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase
description	ABSTRACT Escherichia coli populations undergo repeated replacement of parental genotypes with fitter variants deep in stationary phase. We isolated one such variant, which emerged after 3 weeks of maintaining an E. coli K-12 population in stationary phase. This variant displayed a small colony phenotype and slow growth and was able to outcompete its ancestor over a narrow time window in stationary phase. The variant also shows tolerance to beta-lactam antibiotics, though not previously exposed to the antibiotic. We show that an RpoC(A494V) mutation confers the slow growth and small colony phenotype on this variant. The ability of this mutation to confer a growth advantage in stationary phase depends on the availability of the stationary-phase sigma factor σS. The RpoC(A494V) mutation upregulates the σS regulon. As shown over 20 years ago, early in prolonged stationary phase, σS attenuation, but not complete loss of activity, confers a fitness advantage. Our study shows that later mutations enhance σS activity, either by mutating the gene for σS directly or via mutations such as RpoC(A494V). The balance between the activities of the housekeeping major sigma factor and σS sets up a trade-off between growth and stress tolerance, which is tuned repeatedly during prolonged stationary phase. IMPORTANCE An important general mechanism of a bacterium’s adaptation to its environment involves adjusting the balance between growing fast and tolerating stresses. One paradigm where this plays out is in prolonged stationary phase: early studies showed that attenuation, but not complete elimination, of the general stress response enables early adaptation of the bacterium E. coli to the conditions established about 10 days into stationary phase. We show here that this balance is not static and that it is tilted back in favor of the general stress response about 2 weeks later. This can be established by direct mutations in the master regulator of the general stress response or by mutations in the core RNA polymerase enzyme itself. These conditions can support the development of antibiotic tolerance although the bacterium is not exposed to the antibiotic. Further exploration of the growth-stress balance over the course of stationary phase will necessarily require a deeper understanding of the events in the extracellular milieu.
format	article
author	Pabitra Nandy Savita Chib Aswin Seshasayee
author_facet	Pabitra Nandy Savita Chib Aswin Seshasayee
author_sort	Pabitra Nandy
title	A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase
title_short	A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase
title_full	A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase
title_fullStr	A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase
title_full_unstemmed	A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase
title_sort	mutant rna polymerase activates the general stress response, enabling <named-content content-type="genus-species">escherichia coli</named-content> adaptation to late prolonged stationary phase
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/e46bc44df63349be983049252c95953f
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A Mutant RNA Polymerase Activates the General Stress Response, Enabling <named-content content-type="genus-species">Escherichia coli</named-content> Adaptation to Late Prolonged Stationary Phase

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