RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the most common causative agent of community-acquired urinary tract infection (UTI). In order to cause UTI, UPEC must endure stresses ranging from nutrient limitation to host immune components. RpoS (σS), the general stress response sigma factor, dir...

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Autores principales:	Andrew J. Hryckowian, Rodney A. Welch
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a0f38293919c4d058169f0ab89d026ab
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spelling	oai:doaj.org-article:a0f38293919c4d058169f0ab89d026ab2021-11-15T15:40:23ZRpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT07310.1128/mBio.00023-132150-7511https://doaj.org/article/a0f38293919c4d058169f0ab89d026ab2013-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00023-13https://doaj.org/toc/2150-7511ABSTRACT Uropathogenic Escherichia coli (UPEC) is the most common causative agent of community-acquired urinary tract infection (UTI). In order to cause UTI, UPEC must endure stresses ranging from nutrient limitation to host immune components. RpoS (σS), the general stress response sigma factor, directs gene expression under a variety of inhibitory conditions. Our study of rpoS in UPEC strain CFT073 began after we discovered an rpoS-frameshift mutation in one of our laboratory stocks of “wild-type” CFT073. We demonstrate that an rpoS-deletion mutation in CFT073 leads to a colonization defect during UTI of CBA/J mice at 48 hours postinfection (hpi). There is no difference between the growth rates of CFT073 and CFT073 rpoS in urine. This indicates that rpoS is needed for replication and survival in the host rather than being needed to address limitations imposed by urine nutrients. Consistent with previous observations in E. coli K-12, CFT073 rpoS is more sensitive to oxidative stress than the wild type. We demonstrate that peroxide levels are elevated in voided urine from CFT073-infected mice compared to urine from mock-infected mice, which supports the notion that oxidative stress is generated by the host in response to UPEC. In mice that lack phagocyte oxidase, the enzyme complex expressed by phagocytes that produces superoxide, the competitive defect of CFT073 rpoS in bladder colonization is lost. These results demonstrate that σS is important for UPEC survival under conditions of phagocyte oxidase-generated stress during UTI. Though σS affects the pathogenesis of other bacterial species, this is the first work that directly implicates σS as important for UPEC pathogenesis. IMPORTANCE UPEC must cope with a variety of stressful conditions in the urinary tract during infection. RpoS (σS), the general stress response sigma factor, is known to direct the expression of many genes under a variety of stressful conditions in laboratory-adapted E. coli K-12. Here, we show that σS is needed by the model UPEC strain CFT073 to cope with oxidative stress provided by phagocytes during infection. These findings represent the first report that implicates σS in the fitness of UPEC during infection and support the idea of the need for a better understanding of the effects of this global regulator of gene expression during UTI.Andrew J. HryckowianRodney A. WelchAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 1 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Andrew J. Hryckowian Rodney A. Welch RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073
description	ABSTRACT Uropathogenic Escherichia coli (UPEC) is the most common causative agent of community-acquired urinary tract infection (UTI). In order to cause UTI, UPEC must endure stresses ranging from nutrient limitation to host immune components. RpoS (σS), the general stress response sigma factor, directs gene expression under a variety of inhibitory conditions. Our study of rpoS in UPEC strain CFT073 began after we discovered an rpoS-frameshift mutation in one of our laboratory stocks of “wild-type” CFT073. We demonstrate that an rpoS-deletion mutation in CFT073 leads to a colonization defect during UTI of CBA/J mice at 48 hours postinfection (hpi). There is no difference between the growth rates of CFT073 and CFT073 rpoS in urine. This indicates that rpoS is needed for replication and survival in the host rather than being needed to address limitations imposed by urine nutrients. Consistent with previous observations in E. coli K-12, CFT073 rpoS is more sensitive to oxidative stress than the wild type. We demonstrate that peroxide levels are elevated in voided urine from CFT073-infected mice compared to urine from mock-infected mice, which supports the notion that oxidative stress is generated by the host in response to UPEC. In mice that lack phagocyte oxidase, the enzyme complex expressed by phagocytes that produces superoxide, the competitive defect of CFT073 rpoS in bladder colonization is lost. These results demonstrate that σS is important for UPEC survival under conditions of phagocyte oxidase-generated stress during UTI. Though σS affects the pathogenesis of other bacterial species, this is the first work that directly implicates σS as important for UPEC pathogenesis. IMPORTANCE UPEC must cope with a variety of stressful conditions in the urinary tract during infection. RpoS (σS), the general stress response sigma factor, is known to direct the expression of many genes under a variety of stressful conditions in laboratory-adapted E. coli K-12. Here, we show that σS is needed by the model UPEC strain CFT073 to cope with oxidative stress provided by phagocytes during infection. These findings represent the first report that implicates σS in the fitness of UPEC during infection and support the idea of the need for a better understanding of the effects of this global regulator of gene expression during UTI.
format	article
author	Andrew J. Hryckowian Rodney A. Welch
author_facet	Andrew J. Hryckowian Rodney A. Welch
author_sort	Andrew J. Hryckowian
title	RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073
title_short	RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073
title_full	RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073
title_fullStr	RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073
title_full_unstemmed	RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073
title_sort	rpos contributes to phagocyte oxidase-mediated stress resistance during urinary tract infection by <named-content content-type="genus-species">escherichia coli</named-content> cft073
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/a0f38293919c4d058169f0ab89d026ab
work_keys_str_mv	AT andrewjhryckowian rposcontributestophagocyteoxidasemediatedstressresistanceduringurinarytractinfectionbynamedcontentcontenttypegenusspeciesescherichiacolinamedcontentcft073 AT rodneyawelch rposcontributestophagocyteoxidasemediatedstressresistanceduringurinarytractinfectionbynamedcontentcontenttypegenusspeciesescherichiacolinamedcontentcft073
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RpoS Contributes to Phagocyte Oxidase-Mediated Stress Resistance during Urinary Tract Infection by <named-content content-type="genus-species">Escherichia coli</named-content> CFT073

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