Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>

ABSTRACT Poor clinical outcomes (disfigurement, amputation, and death) and significant economic losses in the aquaculture industry can be attributed to the potent opportunistic human pathogen Vibrio vulnificus. V. vulnificus, as well as the bivalves (oysters) it naturally colonizes, is indigenous to...

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Autores principales:	Daniel M. Chodur, Patrick Coulter, Jacob Isaacs, Meng Pu, Nico Fernandez, Chris M. Waters, Dean A. Rowe-Magnus
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	PAPS Vibrio biofilms c-di-GMP extracellular signaling metabolic regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6ad2c5499cf441d28e802025ccbd1113
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spelling	oai:doaj.org-article:6ad2c5499cf441d28e802025ccbd11132021-11-15T16:00:15ZEnvironmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>10.1128/mBio.01377-182150-7511https://doaj.org/article/6ad2c5499cf441d28e802025ccbd11132018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01377-18https://doaj.org/toc/2150-7511ABSTRACT Poor clinical outcomes (disfigurement, amputation, and death) and significant economic losses in the aquaculture industry can be attributed to the potent opportunistic human pathogen Vibrio vulnificus. V. vulnificus, as well as the bivalves (oysters) it naturally colonizes, is indigenous to estuaries and human-inhabited coastal regions and must endure constantly changing environmental conditions as freshwater and seawater enter, mix, and exit the water column. Elevated cellular c-di-GMP levels trigger biofilm formation, but relatively little is known regarding the environmental signals that initiate this response. Here, we show that calcium is a primary environmental signal that specifically increases intracellular c-di-GMP concentrations, which in turn triggers expression of the brp extracellular polysaccharide that enhances biofilm formation. A transposon screen for the loss of calcium-induced PbrpA expression revealed CysD, an enzyme in the sulfate assimilation pathway. Targeted disruption of the pathway indicated that the production of a specific metabolic intermediate, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), was required for calcium-induced PbrpA expression and that PAPS was separately required for development of the physiologically distinct rugose phenotype. Thus, PAPS behaves as a second messenger in V. vulnificus. Moreover, c-di-GMP and BrpT (the activator of brp expression) acted in concert to bias expression of the sulfate assimilation pathway toward PAPS and c-di-GMP accumulation, establishing a feed-forward regulatory loop to boost brp expression. Thus, this signaling network links extracellular calcium and sulfur availability to the intracellular second messengers PAPS and c-di-GMP in the regulation of V. vulnificus biofilm formation and rugosity, survival phenotypes underpinning its evolution as a resilient environmental organism. IMPORTANCE The second messenger c-di-GMP is a key regulator of bacterial physiology. The V. vulnificus genome encodes nearly 100 proteins predicted to make, break, and bind c-di-GMP. However, relatively little is known regarding the environmental signals that regulate c-di-GMP levels and biofilm formation in V. vulnificus. Here, we identify calcium as a primary environmental signal that specifically increases intracellular c-di-GMP concentrations, which in turn triggers brp-mediated biofilm formation. We show that PAPS, a metabolic intermediate of the sulfate assimilation pathway, acts as a second messenger linking environmental calcium and sulfur source availability to the production of another intracellular second messenger (c-di-GMP) to regulate biofilm and rugose colony formation, developmental pathways that are associated with environmental persistence and efficient bivalve colonization by this potent human pathogen.Daniel M. ChodurPatrick CoulterJacob IsaacsMeng PuNico FernandezChris M. WatersDean A. Rowe-MagnusAmerican Society for MicrobiologyarticlePAPSVibriobiofilmsc-di-GMPextracellular signalingmetabolic regulationMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	PAPS Vibrio biofilms c-di-GMP extracellular signaling metabolic regulation Microbiology QR1-502
spellingShingle	PAPS Vibrio biofilms c-di-GMP extracellular signaling metabolic regulation Microbiology QR1-502 Daniel M. Chodur Patrick Coulter Jacob Isaacs Meng Pu Nico Fernandez Chris M. Waters Dean A. Rowe-Magnus Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>
description	ABSTRACT Poor clinical outcomes (disfigurement, amputation, and death) and significant economic losses in the aquaculture industry can be attributed to the potent opportunistic human pathogen Vibrio vulnificus. V. vulnificus, as well as the bivalves (oysters) it naturally colonizes, is indigenous to estuaries and human-inhabited coastal regions and must endure constantly changing environmental conditions as freshwater and seawater enter, mix, and exit the water column. Elevated cellular c-di-GMP levels trigger biofilm formation, but relatively little is known regarding the environmental signals that initiate this response. Here, we show that calcium is a primary environmental signal that specifically increases intracellular c-di-GMP concentrations, which in turn triggers expression of the brp extracellular polysaccharide that enhances biofilm formation. A transposon screen for the loss of calcium-induced PbrpA expression revealed CysD, an enzyme in the sulfate assimilation pathway. Targeted disruption of the pathway indicated that the production of a specific metabolic intermediate, 3′-phosphoadenosine 5′-phosphosulfate (PAPS), was required for calcium-induced PbrpA expression and that PAPS was separately required for development of the physiologically distinct rugose phenotype. Thus, PAPS behaves as a second messenger in V. vulnificus. Moreover, c-di-GMP and BrpT (the activator of brp expression) acted in concert to bias expression of the sulfate assimilation pathway toward PAPS and c-di-GMP accumulation, establishing a feed-forward regulatory loop to boost brp expression. Thus, this signaling network links extracellular calcium and sulfur availability to the intracellular second messengers PAPS and c-di-GMP in the regulation of V. vulnificus biofilm formation and rugosity, survival phenotypes underpinning its evolution as a resilient environmental organism. IMPORTANCE The second messenger c-di-GMP is a key regulator of bacterial physiology. The V. vulnificus genome encodes nearly 100 proteins predicted to make, break, and bind c-di-GMP. However, relatively little is known regarding the environmental signals that regulate c-di-GMP levels and biofilm formation in V. vulnificus. Here, we identify calcium as a primary environmental signal that specifically increases intracellular c-di-GMP concentrations, which in turn triggers brp-mediated biofilm formation. We show that PAPS, a metabolic intermediate of the sulfate assimilation pathway, acts as a second messenger linking environmental calcium and sulfur source availability to the production of another intracellular second messenger (c-di-GMP) to regulate biofilm and rugose colony formation, developmental pathways that are associated with environmental persistence and efficient bivalve colonization by this potent human pathogen.
format	article
author	Daniel M. Chodur Patrick Coulter Jacob Isaacs Meng Pu Nico Fernandez Chris M. Waters Dean A. Rowe-Magnus
author_facet	Daniel M. Chodur Patrick Coulter Jacob Isaacs Meng Pu Nico Fernandez Chris M. Waters Dean A. Rowe-Magnus
author_sort	Daniel M. Chodur
title	Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_short	Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_full	Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_fullStr	Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_full_unstemmed	Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>
title_sort	environmental calcium initiates a feed-forward signaling circuit that regulates biofilm formation and rugosity in <named-content content-type="genus-species">vibrio vulnificus</named-content>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/6ad2c5499cf441d28e802025ccbd1113
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Environmental Calcium Initiates a Feed-Forward Signaling Circuit That Regulates Biofilm Formation and Rugosity in <named-content content-type="genus-species">Vibrio vulnificus</named-content>

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