Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes

ABSTRACT Vibrio cholerae is a globally important pathogen responsible for the severe epidemic diarrheal disease called cholera. The current and ongoing seventh pandemic of cholera is caused by El Tor strains, which have completely replaced the sixth-pandemic classical strains of V. cholerae. To succ...

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Autores principales:	Florence Caro, José A. Caro, Nicole M. Place, John J. Mekalanos
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	TsrA Vibrio cholerae horizontal gene transfer structural modeling transcriptional regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5f8e487919d5478da56c603b22da86dc
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spelling	oai:doaj.org-article:5f8e487919d5478da56c603b22da86dc2021-11-15T15:55:43ZTranscriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes10.1128/mBio.02901-202150-7511https://doaj.org/article/5f8e487919d5478da56c603b22da86dc2020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02901-20https://doaj.org/toc/2150-7511ABSTRACT Vibrio cholerae is a globally important pathogen responsible for the severe epidemic diarrheal disease called cholera. The current and ongoing seventh pandemic of cholera is caused by El Tor strains, which have completely replaced the sixth-pandemic classical strains of V. cholerae. To successfully establish infection and disseminate to new victims, V. cholerae relies on key virulence factors encoded on horizontally acquired genetic elements. The expression of these factors relies on the regulatory architecture that coordinates the timely expression of virulence determinants during host infection. Here, we apply transcriptomics and structural modeling to understand how type VI secretion system regulator A (TsrA) affects gene expression in both the classical and El Tor biotypes of V. cholerae. We find that TsrA acts as a negative regulator of V. cholerae virulence genes encoded on horizontally acquired genetic elements. The TsrA regulon comprises genes encoding cholera toxin (CT), the toxin-coregulated pilus (TCP), and the type VI secretion system (T6SS), as well as genes involved in biofilm formation. The majority of the TsrA regulon is carried on horizontally acquired AT-rich genetic islands whose loss or acquisition could be directly ascribed to the differences between the classical and El Tor strains studied. Our modeling predicts that the TsrA protein is a structural homolog of the histone-like nucleoid structuring protein (H-NS) oligomerization domain and is likely capable of forming higher-order superhelical structures, potentially with DNA. These findings describe how TsrA can integrate into the intricate V. cholerae virulence gene expression program, controlling gene expression through transcriptional silencing. IMPORTANCE Pathogenic Vibrio cholerae strains express multiple virulence factors that are encoded by bacteriophage and chromosomal islands. These include cholera toxin and the intestinal colonization pilus called the toxin-coregulated pilus, which are essential for causing severe disease in humans. However, it is presently unclear how the expression of these horizontally acquired accessory virulence genes can be efficiently integrated with preexisting transcriptional programs that are presumably fine-tuned for optimal expression in V. cholerae before its conversion to a human pathogen. Here, we report the role of a transcriptional regulator (TsrA) in silencing horizontally acquired genes encoding important virulence factors. We propose that this factor could be critical to the efficient acquisition of accessory virulence genes by silencing their expression until other signals trigger their transcriptional activation within the host.Florence CaroJosé A. CaroNicole M. PlaceJohn J. MekalanosAmerican Society for MicrobiologyarticleTsrAVibrio choleraehorizontal gene transferstructural modelingtranscriptional regulationMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	TsrA Vibrio cholerae horizontal gene transfer structural modeling transcriptional regulation Microbiology QR1-502
spellingShingle	TsrA Vibrio cholerae horizontal gene transfer structural modeling transcriptional regulation Microbiology QR1-502 Florence Caro José A. Caro Nicole M. Place John J. Mekalanos Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes
description	ABSTRACT Vibrio cholerae is a globally important pathogen responsible for the severe epidemic diarrheal disease called cholera. The current and ongoing seventh pandemic of cholera is caused by El Tor strains, which have completely replaced the sixth-pandemic classical strains of V. cholerae. To successfully establish infection and disseminate to new victims, V. cholerae relies on key virulence factors encoded on horizontally acquired genetic elements. The expression of these factors relies on the regulatory architecture that coordinates the timely expression of virulence determinants during host infection. Here, we apply transcriptomics and structural modeling to understand how type VI secretion system regulator A (TsrA) affects gene expression in both the classical and El Tor biotypes of V. cholerae. We find that TsrA acts as a negative regulator of V. cholerae virulence genes encoded on horizontally acquired genetic elements. The TsrA regulon comprises genes encoding cholera toxin (CT), the toxin-coregulated pilus (TCP), and the type VI secretion system (T6SS), as well as genes involved in biofilm formation. The majority of the TsrA regulon is carried on horizontally acquired AT-rich genetic islands whose loss or acquisition could be directly ascribed to the differences between the classical and El Tor strains studied. Our modeling predicts that the TsrA protein is a structural homolog of the histone-like nucleoid structuring protein (H-NS) oligomerization domain and is likely capable of forming higher-order superhelical structures, potentially with DNA. These findings describe how TsrA can integrate into the intricate V. cholerae virulence gene expression program, controlling gene expression through transcriptional silencing. IMPORTANCE Pathogenic Vibrio cholerae strains express multiple virulence factors that are encoded by bacteriophage and chromosomal islands. These include cholera toxin and the intestinal colonization pilus called the toxin-coregulated pilus, which are essential for causing severe disease in humans. However, it is presently unclear how the expression of these horizontally acquired accessory virulence genes can be efficiently integrated with preexisting transcriptional programs that are presumably fine-tuned for optimal expression in V. cholerae before its conversion to a human pathogen. Here, we report the role of a transcriptional regulator (TsrA) in silencing horizontally acquired genes encoding important virulence factors. We propose that this factor could be critical to the efficient acquisition of accessory virulence genes by silencing their expression until other signals trigger their transcriptional activation within the host.
format	article
author	Florence Caro José A. Caro Nicole M. Place John J. Mekalanos
author_facet	Florence Caro José A. Caro Nicole M. Place John J. Mekalanos
author_sort	Florence Caro
title	Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes
title_short	Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes
title_full	Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes
title_fullStr	Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes
title_full_unstemmed	Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes
title_sort	transcriptional silencing by tsra in the evolution of pathogenic <named-content content-type="genus-species">vibrio cholerae</named-content> biotypes
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/5f8e487919d5478da56c603b22da86dc
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Transcriptional Silencing by TsrA in the Evolution of Pathogenic <named-content content-type="genus-species">Vibrio cholerae</named-content> Biotypes

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