Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>

ABSTRACT Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relat...

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Autores principales:	Roberto C. Molina-Quiroz, Cecilia Silva-Valenzuela, Jennifer Brewster, Eduardo Castro-Nallar, Stuart B. Levy, Andrew Camilli
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	CRP DNA damage SOS response Tn-Seq antibiotics cAMP Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/23bd5a2c1b5b4ff488e41f203d8f40f2
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spelling	oai:doaj.org-article:23bd5a2c1b5b4ff488e41f203d8f40f22021-11-15T15:53:26ZCyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>10.1128/mBio.02144-172150-7511https://doaj.org/article/23bd5a2c1b5b4ff488e41f203d8f40f22018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02144-17https://doaj.org/toc/2150-7511ABSTRACT Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli, as measured by survival after exposure to a β-lactam antibiotic. This phenotype is regulated by a set of genes leading to an oxidative stress response and SOS-dependent DNA repair. Thus, persister cells tolerant to cell wall-acting antibiotics must cope with oxidative stress and DNA damage and these processes are regulated by cyclic AMP in uropathogenic E. coli. IMPORTANCE Bacterial persister cells are important in relapsing infections in patients treated with antibiotics and also in the emergence of antibiotic resistance. Our results show that in uropathogenic E. coli, the second messenger cyclic AMP negatively regulates persister cell formation, since in its absence much more persister cells form that are tolerant to β-lactams antibiotics. We reveal the mechanism to be decreased levels of reactive oxygen species, specifically hydroxyl radicals, and SOS-dependent DNA repair. Our findings suggest that the oxidative stress response and DNA repair are relevant pathways to target in the design of persister-specific antibiotic compounds.Roberto C. Molina-QuirozCecilia Silva-ValenzuelaJennifer BrewsterEduardo Castro-NallarStuart B. LevyAndrew CamilliAmerican Society for MicrobiologyarticleCRPDNA damageSOS responseTn-SeqantibioticscAMPMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	CRP DNA damage SOS response Tn-Seq antibiotics cAMP Microbiology QR1-502
spellingShingle	CRP DNA damage SOS response Tn-Seq antibiotics cAMP Microbiology QR1-502 Roberto C. Molina-Quiroz Cecilia Silva-Valenzuela Jennifer Brewster Eduardo Castro-Nallar Stuart B. Levy Andrew Camilli Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>
description	ABSTRACT Bacterial persistence is a transient, nonheritable physiological state that provides tolerance to bactericidal antibiotics. The stringent response, toxin-antitoxin modules, and stochastic processes, among other mechanisms, play roles in this phenomenon. How persistence is regulated is relatively ill defined. Here we show that cyclic AMP, a global regulator of carbon catabolism and other core processes, is a negative regulator of bacterial persistence in uropathogenic Escherichia coli, as measured by survival after exposure to a β-lactam antibiotic. This phenotype is regulated by a set of genes leading to an oxidative stress response and SOS-dependent DNA repair. Thus, persister cells tolerant to cell wall-acting antibiotics must cope with oxidative stress and DNA damage and these processes are regulated by cyclic AMP in uropathogenic E. coli. IMPORTANCE Bacterial persister cells are important in relapsing infections in patients treated with antibiotics and also in the emergence of antibiotic resistance. Our results show that in uropathogenic E. coli, the second messenger cyclic AMP negatively regulates persister cell formation, since in its absence much more persister cells form that are tolerant to β-lactams antibiotics. We reveal the mechanism to be decreased levels of reactive oxygen species, specifically hydroxyl radicals, and SOS-dependent DNA repair. Our findings suggest that the oxidative stress response and DNA repair are relevant pathways to target in the design of persister-specific antibiotic compounds.
format	article
author	Roberto C. Molina-Quiroz Cecilia Silva-Valenzuela Jennifer Brewster Eduardo Castro-Nallar Stuart B. Levy Andrew Camilli
author_facet	Roberto C. Molina-Quiroz Cecilia Silva-Valenzuela Jennifer Brewster Eduardo Castro-Nallar Stuart B. Levy Andrew Camilli
author_sort	Roberto C. Molina-Quiroz
title	Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>
title_short	Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>
title_full	Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>
title_fullStr	Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>
title_full_unstemmed	Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>
title_sort	cyclic amp regulates bacterial persistence through repression of the oxidative stress response and sos-dependent dna repair in uropathogenic <italic toggle="yes">escherichia coli</italic>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/23bd5a2c1b5b4ff488e41f203d8f40f2
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Cyclic AMP Regulates Bacterial Persistence through Repression of the Oxidative Stress Response and SOS-Dependent DNA Repair in Uropathogenic <italic toggle="yes">Escherichia coli</italic>

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