A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.

A fundamental, but unanswered question in host-pathogen interactions is the timing, localization and population distribution of virulence gene expression during infection. Here, microarray and in situ single cell expression methods were used to study Vibrio cholerae growth and virulence gene express...

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Autores principales:	Alex T Nielsen, Nadia A Dolganov, Thomas Rasmussen, Glen Otto, Michael C Miller, Stephen A Felt, Stéphanie Torreilles, Gary K Schoolnik
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3486c90edb2b40dcb9e23dfdd89ec4fe
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spelling	oai:doaj.org-article:3486c90edb2b40dcb9e23dfdd89ec4fe2021-11-18T06:01:36ZA bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.1553-73661553-737410.1371/journal.ppat.1001102https://doaj.org/article/3486c90edb2b40dcb9e23dfdd89ec4fe2010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20862321/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374A fundamental, but unanswered question in host-pathogen interactions is the timing, localization and population distribution of virulence gene expression during infection. Here, microarray and in situ single cell expression methods were used to study Vibrio cholerae growth and virulence gene expression during infection of the rabbit ligated ileal loop model of cholera. Genes encoding the toxin-coregulated pilus (TCP) and cholera toxin (CT) were powerfully expressed early in the infectious process in bacteria adjacent to epithelial surfaces. Increased growth was found to co-localize with virulence gene expression. Significant heterogeneity in the expression of tcpA, the repeating subunit of TCP, was observed late in the infectious process. The expression of tcpA, studied in single cells in a homogeneous medium, demonstrated unimodal induction of tcpA after addition of bicarbonate, a chemical inducer of virulence gene expression. Striking bifurcation of the population occurred during entry into stationary phase: one subpopulation continued to express tcpA, whereas the expression declined in the other subpopulation. ctxA, encoding the A subunit of CT, and toxT, encoding the proximal master regulator of virulence gene expression also exhibited the bifurcation phenotype. The bifurcation phenotype was found to be reversible, epigenetic and to persist after removal of bicarbonate, features consistent with bistable switches. The bistable switch requires the positive-feedback circuit controlling ToxT expression and formation of the CRP-cAMP complex during entry into stationary phase. Key features of this bistable switch also were demonstrated in vivo, where striking heterogeneity in tcpA expression was observed in luminal fluid in later stages of the infection. When this fluid was diluted into artificial seawater, bacterial aggregates continued to express tcpA for prolonged periods of time. The bistable control of virulence gene expression points to a mechanism that could generate a subpopulation of V. cholerae that continues to produce TCP and CT in the rice water stools of cholera patients.Alex T NielsenNadia A DolganovThomas RasmussenGlen OttoMichael C MillerStephen A FeltStéphanie TorreillesGary K SchoolnikPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 9, p e1001102 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Alex T Nielsen Nadia A Dolganov Thomas Rasmussen Glen Otto Michael C Miller Stephen A Felt Stéphanie Torreilles Gary K Schoolnik A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.
description	A fundamental, but unanswered question in host-pathogen interactions is the timing, localization and population distribution of virulence gene expression during infection. Here, microarray and in situ single cell expression methods were used to study Vibrio cholerae growth and virulence gene expression during infection of the rabbit ligated ileal loop model of cholera. Genes encoding the toxin-coregulated pilus (TCP) and cholera toxin (CT) were powerfully expressed early in the infectious process in bacteria adjacent to epithelial surfaces. Increased growth was found to co-localize with virulence gene expression. Significant heterogeneity in the expression of tcpA, the repeating subunit of TCP, was observed late in the infectious process. The expression of tcpA, studied in single cells in a homogeneous medium, demonstrated unimodal induction of tcpA after addition of bicarbonate, a chemical inducer of virulence gene expression. Striking bifurcation of the population occurred during entry into stationary phase: one subpopulation continued to express tcpA, whereas the expression declined in the other subpopulation. ctxA, encoding the A subunit of CT, and toxT, encoding the proximal master regulator of virulence gene expression also exhibited the bifurcation phenotype. The bifurcation phenotype was found to be reversible, epigenetic and to persist after removal of bicarbonate, features consistent with bistable switches. The bistable switch requires the positive-feedback circuit controlling ToxT expression and formation of the CRP-cAMP complex during entry into stationary phase. Key features of this bistable switch also were demonstrated in vivo, where striking heterogeneity in tcpA expression was observed in luminal fluid in later stages of the infection. When this fluid was diluted into artificial seawater, bacterial aggregates continued to express tcpA for prolonged periods of time. The bistable control of virulence gene expression points to a mechanism that could generate a subpopulation of V. cholerae that continues to produce TCP and CT in the rice water stools of cholera patients.
format	article
author	Alex T Nielsen Nadia A Dolganov Thomas Rasmussen Glen Otto Michael C Miller Stephen A Felt Stéphanie Torreilles Gary K Schoolnik
author_facet	Alex T Nielsen Nadia A Dolganov Thomas Rasmussen Glen Otto Michael C Miller Stephen A Felt Stéphanie Torreilles Gary K Schoolnik
author_sort	Alex T Nielsen
title	A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.
title_short	A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.
title_full	A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.
title_fullStr	A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.
title_full_unstemmed	A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.
title_sort	bistable switch and anatomical site control vibrio cholerae virulence gene expression in the intestine.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/3486c90edb2b40dcb9e23dfdd89ec4fe
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A bistable switch and anatomical site control Vibrio cholerae virulence gene expression in the intestine.

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