Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine

ABSTRACT The Vibrio cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that coordinates the bacterial response to carbohydrate availability through direct interactions of its components with protein targets. One such component, gl...

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Autores principales:	Vidhya Vijayakumar, Audrey S. Vanhove, Bradley S. Pickering, Julie Liao, Braden T. Tierney, John M. Asara, Roderick Bronson, Paula I. Watnick
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Vibrio cholerae amphipathic helix biofilms phosphoenolpyruvate phosphotransferase system sugar transport Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6c0aa28be84747858d028bbc6da32d6c
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spelling	oai:doaj.org-article:6c0aa28be84747858d028bbc6da32d6c2021-11-15T15:58:21ZRemoval of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine10.1128/mBio.00858-182150-7511https://doaj.org/article/6c0aa28be84747858d028bbc6da32d6c2018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00858-18https://doaj.org/toc/2150-7511ABSTRACT The Vibrio cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that coordinates the bacterial response to carbohydrate availability through direct interactions of its components with protein targets. One such component, glucose-specific enzyme IIA (EIIAGlc), is a master regulator that coordinates bacterial metabolism, nutrient uptake, and behavior by direct interactions with cytoplasmic and membrane-associated protein partners. Here, we show that an amphipathic helix (AH) at the N terminus of V. cholerae EIIAGlc serves as a membrane association domain that is dispensable for interactions with cytoplasmic partners but essential for regulation of integral membrane protein partners. By deleting this AH, we reveal previously unappreciated opposing regulatory functions for EIIAGlc at the membrane and in the cytoplasm and show that these opposing functions are active in the laboratory biofilm and the mammalian intestine. Phosphotransfer through the PTS proceeds in the absence of the EIIAGlc AH, while PTS-dependent sugar transport is blocked. This demonstrates that the AH couples phosphotransfer to sugar transport and refutes the paradigm of EIIAGlc as a simple phosphotransfer component in PTS-dependent transport. Our findings show that Vibrio cholerae EIIAGlc, a central regulator of pathogen metabolism, contributes to optimization of bacterial physiology by integrating metabolic cues arising from the cytoplasm with nutritional cues arising from the environment. Because pathogen carbon metabolism alters the intestinal environment, we propose that it may be manipulated to minimize the metabolic cost of intestinal infection. IMPORTANCE The V. cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that regulates cellular physiology and virulence in response to nutritional signals. Glucose-specific enzyme IIA (EIIAGlc), a component of the PTS, is a master regulator that coordinates bacterial metabolism, nutrient uptake, and behavior by direct interactions with protein partners. We show that an amphipathic helix (AH) at the N terminus of V. cholerae EIIAGlc serves as a membrane association domain that is dispensable for interactions with cytoplasmic partners but essential for regulation of integral membrane protein partners. By removing this amphipathic helix, hidden, opposing roles for cytoplasmic partners of EIIAGlc in both biofilm formation and metabolism within the mammalian intestine are revealed. This study defines a novel paradigm for AH function in integrating opposing regulatory functions in the cytoplasm and at the bacterial cell membrane and highlights the PTS as a target for metabolic modulation of the intestinal environment.Vidhya VijayakumarAudrey S. VanhoveBradley S. PickeringJulie LiaoBraden T. TierneyJohn M. AsaraRoderick BronsonPaula I. WatnickAmerican Society for MicrobiologyarticleVibrio choleraeamphipathic helixbiofilmsphosphoenolpyruvate phosphotransferase systemsugar transportMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Vibrio cholerae amphipathic helix biofilms phosphoenolpyruvate phosphotransferase system sugar transport Microbiology QR1-502
spellingShingle	Vibrio cholerae amphipathic helix biofilms phosphoenolpyruvate phosphotransferase system sugar transport Microbiology QR1-502 Vidhya Vijayakumar Audrey S. Vanhove Bradley S. Pickering Julie Liao Braden T. Tierney John M. Asara Roderick Bronson Paula I. Watnick Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine
description	ABSTRACT The Vibrio cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that coordinates the bacterial response to carbohydrate availability through direct interactions of its components with protein targets. One such component, glucose-specific enzyme IIA (EIIAGlc), is a master regulator that coordinates bacterial metabolism, nutrient uptake, and behavior by direct interactions with cytoplasmic and membrane-associated protein partners. Here, we show that an amphipathic helix (AH) at the N terminus of V. cholerae EIIAGlc serves as a membrane association domain that is dispensable for interactions with cytoplasmic partners but essential for regulation of integral membrane protein partners. By deleting this AH, we reveal previously unappreciated opposing regulatory functions for EIIAGlc at the membrane and in the cytoplasm and show that these opposing functions are active in the laboratory biofilm and the mammalian intestine. Phosphotransfer through the PTS proceeds in the absence of the EIIAGlc AH, while PTS-dependent sugar transport is blocked. This demonstrates that the AH couples phosphotransfer to sugar transport and refutes the paradigm of EIIAGlc as a simple phosphotransfer component in PTS-dependent transport. Our findings show that Vibrio cholerae EIIAGlc, a central regulator of pathogen metabolism, contributes to optimization of bacterial physiology by integrating metabolic cues arising from the cytoplasm with nutritional cues arising from the environment. Because pathogen carbon metabolism alters the intestinal environment, we propose that it may be manipulated to minimize the metabolic cost of intestinal infection. IMPORTANCE The V. cholerae phosphoenolpyruvate phosphotransferase system (PTS) is a well-conserved, multicomponent phosphotransfer cascade that regulates cellular physiology and virulence in response to nutritional signals. Glucose-specific enzyme IIA (EIIAGlc), a component of the PTS, is a master regulator that coordinates bacterial metabolism, nutrient uptake, and behavior by direct interactions with protein partners. We show that an amphipathic helix (AH) at the N terminus of V. cholerae EIIAGlc serves as a membrane association domain that is dispensable for interactions with cytoplasmic partners but essential for regulation of integral membrane protein partners. By removing this amphipathic helix, hidden, opposing roles for cytoplasmic partners of EIIAGlc in both biofilm formation and metabolism within the mammalian intestine are revealed. This study defines a novel paradigm for AH function in integrating opposing regulatory functions in the cytoplasm and at the bacterial cell membrane and highlights the PTS as a target for metabolic modulation of the intestinal environment.
format	article
author	Vidhya Vijayakumar Audrey S. Vanhove Bradley S. Pickering Julie Liao Braden T. Tierney John M. Asara Roderick Bronson Paula I. Watnick
author_facet	Vidhya Vijayakumar Audrey S. Vanhove Bradley S. Pickering Julie Liao Braden T. Tierney John M. Asara Roderick Bronson Paula I. Watnick
author_sort	Vidhya Vijayakumar
title	Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine
title_short	Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine
title_full	Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine
title_fullStr	Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine
title_full_unstemmed	Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine
title_sort	removal of a membrane anchor reveals the opposing regulatory functions of <named-content content-type="genus-species">vibrio cholerae</named-content> glucose-specific enzyme iia in biofilms and the mammalian intestine
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/6c0aa28be84747858d028bbc6da32d6c
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Removal of a Membrane Anchor Reveals the Opposing Regulatory Functions of <named-content content-type="genus-species">Vibrio cholerae</named-content> Glucose-Specific Enzyme IIA in Biofilms and the Mammalian Intestine

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