Indole Signaling at the Host-Microbiota-Pathogen Interface

ABSTRACT Microbial establishment within the gastrointestinal (GI) tract requires surveillance of the gut biogeography. The gut microbiota coordinates behaviors by sensing host- or microbiota-derived signals. Here we show for the first time that microbiota-derived indole is highly prevalent in the lu...

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Autores principales:	Aman Kumar, Vanessa Sperandio
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Citrobacter rodentium CpxA indole enterohemorrhagic E. coli (EHEC) locus of enterocyte effacement (LEE) microbiota Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/cce14c8d85dc4beea7308bbc1d6671a0
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spelling	oai:doaj.org-article:cce14c8d85dc4beea7308bbc1d6671a02021-11-15T15:55:25ZIndole Signaling at the Host-Microbiota-Pathogen Interface10.1128/mBio.01031-192150-7511https://doaj.org/article/cce14c8d85dc4beea7308bbc1d6671a02019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01031-19https://doaj.org/toc/2150-7511ABSTRACT Microbial establishment within the gastrointestinal (GI) tract requires surveillance of the gut biogeography. The gut microbiota coordinates behaviors by sensing host- or microbiota-derived signals. Here we show for the first time that microbiota-derived indole is highly prevalent in the lumen compared to the intestinal tissue. This difference in indole concentration plays a key role in modulating virulence gene expression of the enteric pathogens enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium. Indole decreases expression of genes within the locus of enterocyte effacement (LEE) pathogenicity island, which is essential for these pathogens to form attaching and effacing (AE) lesions on enterocytes. We synthetically altered the concentration of indole in the GI tracts of mice by employing mice treated with antibiotics to deplete the microbiota and reconstituted with indole-producing commensal Bacteroides thetaiotaomicron (B. theta) or a B. theta ΔtnaA mutant (does not produce indole) or by engineering an indole-producing C. rodentium strain. This allowed us to assess the role of self-produced versus microbiota-produced indole, and the results show that decreased indole concentrations promote bacterial pathogenesis, while increased levels of indole decrease bacterial virulence gene expression. Moreover, we identified the bacterial membrane-bound histidine sensor kinase (HK) CpxA as an indole sensor. Enteric pathogens sense a gradient of indole concentrations in the gut to probe different niches and successfully establish an infection. IMPORTANCE Pathogens sense and respond to several small molecules within the GI tract to modulate expression of their virulence repertoire. Indole is a signaling molecule produced by the gut microbiota. Here we show that indole concentrations are higher in the lumen, where the microbiota is present, than in the intestinal tissue. The enteric pathogens EHEC and C. rodentium sense indole to downregulate expression of their virulence genes, as a read-out of the luminal compartment. We also identified the bacterial membrane-bound HK CpxA as an indole sensor. This regulation ensures that EHEC and C. rodentium express their virulence genes only at the epithelial lining, which is the niche they colonize.Aman KumarVanessa SperandioAmerican Society for MicrobiologyarticleCitrobacter rodentiumCpxAindoleenterohemorrhagic E. coli (EHEC)locus of enterocyte effacement (LEE)microbiotaMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Citrobacter rodentium CpxA indole enterohemorrhagic E. coli (EHEC) locus of enterocyte effacement (LEE) microbiota Microbiology QR1-502
spellingShingle	Citrobacter rodentium CpxA indole enterohemorrhagic E. coli (EHEC) locus of enterocyte effacement (LEE) microbiota Microbiology QR1-502 Aman Kumar Vanessa Sperandio Indole Signaling at the Host-Microbiota-Pathogen Interface
description	ABSTRACT Microbial establishment within the gastrointestinal (GI) tract requires surveillance of the gut biogeography. The gut microbiota coordinates behaviors by sensing host- or microbiota-derived signals. Here we show for the first time that microbiota-derived indole is highly prevalent in the lumen compared to the intestinal tissue. This difference in indole concentration plays a key role in modulating virulence gene expression of the enteric pathogens enterohemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium. Indole decreases expression of genes within the locus of enterocyte effacement (LEE) pathogenicity island, which is essential for these pathogens to form attaching and effacing (AE) lesions on enterocytes. We synthetically altered the concentration of indole in the GI tracts of mice by employing mice treated with antibiotics to deplete the microbiota and reconstituted with indole-producing commensal Bacteroides thetaiotaomicron (B. theta) or a B. theta ΔtnaA mutant (does not produce indole) or by engineering an indole-producing C. rodentium strain. This allowed us to assess the role of self-produced versus microbiota-produced indole, and the results show that decreased indole concentrations promote bacterial pathogenesis, while increased levels of indole decrease bacterial virulence gene expression. Moreover, we identified the bacterial membrane-bound histidine sensor kinase (HK) CpxA as an indole sensor. Enteric pathogens sense a gradient of indole concentrations in the gut to probe different niches and successfully establish an infection. IMPORTANCE Pathogens sense and respond to several small molecules within the GI tract to modulate expression of their virulence repertoire. Indole is a signaling molecule produced by the gut microbiota. Here we show that indole concentrations are higher in the lumen, where the microbiota is present, than in the intestinal tissue. The enteric pathogens EHEC and C. rodentium sense indole to downregulate expression of their virulence genes, as a read-out of the luminal compartment. We also identified the bacterial membrane-bound HK CpxA as an indole sensor. This regulation ensures that EHEC and C. rodentium express their virulence genes only at the epithelial lining, which is the niche they colonize.
format	article
author	Aman Kumar Vanessa Sperandio
author_facet	Aman Kumar Vanessa Sperandio
author_sort	Aman Kumar
title	Indole Signaling at the Host-Microbiota-Pathogen Interface
title_short	Indole Signaling at the Host-Microbiota-Pathogen Interface
title_full	Indole Signaling at the Host-Microbiota-Pathogen Interface
title_fullStr	Indole Signaling at the Host-Microbiota-Pathogen Interface
title_full_unstemmed	Indole Signaling at the Host-Microbiota-Pathogen Interface
title_sort	indole signaling at the host-microbiota-pathogen interface
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/cce14c8d85dc4beea7308bbc1d6671a0
work_keys_str_mv	AT amankumar indolesignalingatthehostmicrobiotapathogeninterface AT vanessasperandio indolesignalingatthehostmicrobiotapathogeninterface
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Indole Signaling at the Host-Microbiota-Pathogen Interface

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