Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis

ABSTRACT Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic...

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Autores principales:	Matt S. Conover, Maria Hadjifrangiskou, Joseph J. Palermo, Michael E. Hibbing, Karen W. Dodson, Scott J. Hultgren
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/f6b8f3861da246f0b41276a74d832bad
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spelling	oai:doaj.org-article:f6b8f3861da246f0b41276a74d832bad2021-11-15T15:41:41ZMetabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis10.1128/mBio.00104-162150-7511https://doaj.org/article/f6b8f3861da246f0b41276a74d832bad2016-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00104-16https://doaj.org/toc/2150-7511ABSTRACT Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic process, and escape into the host cell cytoplasm. The internalized UPEC can clonally replicate into biofilm-like intracellular bacterial communities (IBCs) of thousands of bacteria while avoiding many host clearance mechanisms. Importantly, IBCs have been documented in urine from women and children suffering acute UTI. To understand this protected bacterial niche, we elucidated the transcriptional profile of bacteria within IBCs using microarrays. We delineated the upregulation within the IBC of genes involved in iron acquisition, metabolism, and transport. Interestingly, lacZ was highly upregulated, suggesting that bacteria were sensing and/or utilizing a galactoside for metabolism in the IBC. A ΔlacZ strain displayed significantly smaller IBCs than the wild-type strain and was attenuated during competitive infection with a wild-type strain. Similarly, a galK mutant resulted in smaller IBCs and attenuated infection. Further, analysis of the highly upregulated gene yeaR revealed that this gene contributes to oxidative stress resistance and type 1 pilus production. These results suggest that bacteria within the IBC are under oxidative stress and, consistent with previous reports, utilize nonglucose carbon metabolites. Better understanding of the bacterial mechanisms used for IBC development and establishment of infection may give insights into development of novel anti-virulence strategies. IMPORTANCE Urinary tract infections (UTIs) are one of the most common bacterial infections, impacting mostly women. Every year, millions of UTIs occur in the U.S. with most being caused by uropathogenic E. coli (UPEC). During a UTI, UPEC invade bladder cells and form an intracellular bacterial community (IBC) that allows for the bacteria to replicate protected from the host immune response. In this study, we investigated genes that are expressed by UPEC within the IBC and determined how they contribute to the formation of this specialized community. Our findings suggest that galactose is important for UPEC growth in the IBC. Additionally, we found that a gene involved in oxidative stress is also important in the regulation of a key factor needed for UPEC invasion of bladder cells. These results may open the door for the development of treatments to diminish UTI frequency and/or severity.Matt S. ConoverMaria HadjifrangiskouJoseph J. PalermoMichael E. HibbingKaren W. DodsonScott J. HultgrenAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 2 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Matt S. Conover Maria Hadjifrangiskou Joseph J. Palermo Michael E. Hibbing Karen W. Dodson Scott J. Hultgren Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis
description	ABSTRACT Uropathogenic Escherichia coli (UPEC) is the primary etiological agent of over 85% of community-acquired urinary tract infections (UTIs). Mouse models of infection have shown that UPEC can invade bladder epithelial cells in a type 1 pilus-dependent mechanism, avoid a TLR4-mediated exocytic process, and escape into the host cell cytoplasm. The internalized UPEC can clonally replicate into biofilm-like intracellular bacterial communities (IBCs) of thousands of bacteria while avoiding many host clearance mechanisms. Importantly, IBCs have been documented in urine from women and children suffering acute UTI. To understand this protected bacterial niche, we elucidated the transcriptional profile of bacteria within IBCs using microarrays. We delineated the upregulation within the IBC of genes involved in iron acquisition, metabolism, and transport. Interestingly, lacZ was highly upregulated, suggesting that bacteria were sensing and/or utilizing a galactoside for metabolism in the IBC. A ΔlacZ strain displayed significantly smaller IBCs than the wild-type strain and was attenuated during competitive infection with a wild-type strain. Similarly, a galK mutant resulted in smaller IBCs and attenuated infection. Further, analysis of the highly upregulated gene yeaR revealed that this gene contributes to oxidative stress resistance and type 1 pilus production. These results suggest that bacteria within the IBC are under oxidative stress and, consistent with previous reports, utilize nonglucose carbon metabolites. Better understanding of the bacterial mechanisms used for IBC development and establishment of infection may give insights into development of novel anti-virulence strategies. IMPORTANCE Urinary tract infections (UTIs) are one of the most common bacterial infections, impacting mostly women. Every year, millions of UTIs occur in the U.S. with most being caused by uropathogenic E. coli (UPEC). During a UTI, UPEC invade bladder cells and form an intracellular bacterial community (IBC) that allows for the bacteria to replicate protected from the host immune response. In this study, we investigated genes that are expressed by UPEC within the IBC and determined how they contribute to the formation of this specialized community. Our findings suggest that galactose is important for UPEC growth in the IBC. Additionally, we found that a gene involved in oxidative stress is also important in the regulation of a key factor needed for UPEC invasion of bladder cells. These results may open the door for the development of treatments to diminish UTI frequency and/or severity.
format	article
author	Matt S. Conover Maria Hadjifrangiskou Joseph J. Palermo Michael E. Hibbing Karen W. Dodson Scott J. Hultgren
author_facet	Matt S. Conover Maria Hadjifrangiskou Joseph J. Palermo Michael E. Hibbing Karen W. Dodson Scott J. Hultgren
author_sort	Matt S. Conover
title	Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis
title_short	Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis
title_full	Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis
title_fullStr	Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis
title_full_unstemmed	Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis
title_sort	metabolic requirements of <named-content content-type="genus-species">escherichia coli</named-content> in intracellular bacterial communities during urinary tract infection pathogenesis
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/f6b8f3861da246f0b41276a74d832bad
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Metabolic Requirements of <named-content content-type="genus-species">Escherichia coli</named-content> in Intracellular Bacterial Communities during Urinary Tract Infection Pathogenesis

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