Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>

ABSTRACT Enteric pathogens have complex interactions with the gut microbiota. Most of what is known about them has focused on microbiota-derived metabolites or small molecules that serve as nutrients and/or signals to aid in growth or transcriptionally regulate virulence gene expression. A common vi...

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Autores principales:	Elizabeth A. Cameron, Meredith M. Curtis, Aman Kumar, Gary M. Dunny, Vanessa Sperandio
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	EspP Bacteroides enterohemorrhagic E. coli (EHEC) microbiota type three secretion Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/40a86f55f42747eabee769091e38ae64
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spelling	oai:doaj.org-article:40a86f55f42747eabee769091e38ae642021-11-15T15:52:19ZMicrobiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>10.1128/mBio.02204-182150-7511https://doaj.org/article/40a86f55f42747eabee769091e38ae642018-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02204-18https://doaj.org/toc/2150-7511ABSTRACT Enteric pathogens have complex interactions with the gut microbiota. Most of what is known about them has focused on microbiota-derived metabolites or small molecules that serve as nutrients and/or signals to aid in growth or transcriptionally regulate virulence gene expression. A common virulence strategy is to express a type III secretion system (T3SS), which is a molecular syringe deployed by many Gram-negative pathogens to hijack host cell function. Enterohemorrhagic Escherichia coli (EHEC) requires its T3SS to colonize the intestinal tract and cause disease. Here we report that a prominent member of the intestinal microbiota, Bacteroides thetaiotamicron (Bt), secretes proteases that cleave the translocon of the T3SS of EHEC to enhance effector translocation into host cells. This is in contrast from an endogenous protease from EHEC itself (namely, EspP) that cleaves the translocon protein EspB in a different site to limit effector translocation. The EspB protein forms the T3SS pore in mammalian cells, and pore proteins are conserved in the T3SSs from several pathogens. This is the first demonstration of a commensal species directly processing a pathogen’s T3SS, posing a new paradigm for how the microbiota can influence the severity of disease caused by bacterial pathogens. Because T3SSs are employed by many pathogens, this phenomenon has broad implications to commensal-pathogen relationships. IMPORTANCE The gut microbiota is usually regarded as providing colonization resistance against enteric pathogens. However, some pathogens evolved to thrive with the aid of certain members of the microbiota. Several Gram-negative bacteria employ type three secretion systems (T3SSs), which are molecular syringes that deliver effector proteins to host cells, hijacking host cell function. Here we show that the T3SS of enterohemorrhagic E. coli (EHEC) is cleaved by self and microbiota-derived proteases. Self-cleavage limits effector translocation, while cleavage by the microbiota member Bacteroides thetaiotamicron (Bt) exacerbates effector translocation and lesion formation on epithelial cells.Elizabeth A. CameronMeredith M. CurtisAman KumarGary M. DunnyVanessa SperandioAmerican Society for MicrobiologyarticleEspPBacteroidesenterohemorrhagic E. coli (EHEC)microbiotatype three secretionMicrobiologyQR1-502ENmBio, Vol 9, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	EspP Bacteroides enterohemorrhagic E. coli (EHEC) microbiota type three secretion Microbiology QR1-502
spellingShingle	EspP Bacteroides enterohemorrhagic E. coli (EHEC) microbiota type three secretion Microbiology QR1-502 Elizabeth A. Cameron Meredith M. Curtis Aman Kumar Gary M. Dunny Vanessa Sperandio Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>
description	ABSTRACT Enteric pathogens have complex interactions with the gut microbiota. Most of what is known about them has focused on microbiota-derived metabolites or small molecules that serve as nutrients and/or signals to aid in growth or transcriptionally regulate virulence gene expression. A common virulence strategy is to express a type III secretion system (T3SS), which is a molecular syringe deployed by many Gram-negative pathogens to hijack host cell function. Enterohemorrhagic Escherichia coli (EHEC) requires its T3SS to colonize the intestinal tract and cause disease. Here we report that a prominent member of the intestinal microbiota, Bacteroides thetaiotamicron (Bt), secretes proteases that cleave the translocon of the T3SS of EHEC to enhance effector translocation into host cells. This is in contrast from an endogenous protease from EHEC itself (namely, EspP) that cleaves the translocon protein EspB in a different site to limit effector translocation. The EspB protein forms the T3SS pore in mammalian cells, and pore proteins are conserved in the T3SSs from several pathogens. This is the first demonstration of a commensal species directly processing a pathogen’s T3SS, posing a new paradigm for how the microbiota can influence the severity of disease caused by bacterial pathogens. Because T3SSs are employed by many pathogens, this phenomenon has broad implications to commensal-pathogen relationships. IMPORTANCE The gut microbiota is usually regarded as providing colonization resistance against enteric pathogens. However, some pathogens evolved to thrive with the aid of certain members of the microbiota. Several Gram-negative bacteria employ type three secretion systems (T3SSs), which are molecular syringes that deliver effector proteins to host cells, hijacking host cell function. Here we show that the T3SS of enterohemorrhagic E. coli (EHEC) is cleaved by self and microbiota-derived proteases. Self-cleavage limits effector translocation, while cleavage by the microbiota member Bacteroides thetaiotamicron (Bt) exacerbates effector translocation and lesion formation on epithelial cells.
format	article
author	Elizabeth A. Cameron Meredith M. Curtis Aman Kumar Gary M. Dunny Vanessa Sperandio
author_facet	Elizabeth A. Cameron Meredith M. Curtis Aman Kumar Gary M. Dunny Vanessa Sperandio
author_sort	Elizabeth A. Cameron
title	Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>
title_short	Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>
title_full	Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>
title_fullStr	Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>
title_full_unstemmed	Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>
title_sort	microbiota and pathogen proteases modulate type iii secretion activity in enterohemorrhagic <named-content content-type="genus-species">escherichia coli</named-content>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/40a86f55f42747eabee769091e38ae64
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Microbiota and Pathogen Proteases Modulate Type III Secretion Activity in Enterohemorrhagic <named-content content-type="genus-species">Escherichia coli</named-content>

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