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Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae

Sensing and responding to environmental changes is essential for bacteria to adapt and thrive, and nucleotide-derived second messengers are central signaling systems in this process. The most recently identified bacterial cyclic dinucleotide second messenger, 3′, 3′-cyclic GMP-AMP (cGAMP), was first...

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Autores principales: Severin, Geoffrey B., Ramliden, Miriam S., Hawver, Lisa A., Wang, Kun, Pell, Macy E., Kieninger, Ann-Katrin, Khataokar, Atul, O’Hara, Brendan J., Behrmann, Lara V., Neiditch, Matthew B., Benning, Christoph, Waters, Christopher M., Ng, Wai-Leung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042076/
https://www.ncbi.nlm.nih.gov/pubmed/29891656
http://dx.doi.org/10.1073/pnas.1801233115
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author Severin, Geoffrey B.
Ramliden, Miriam S.
Hawver, Lisa A.
Wang, Kun
Pell, Macy E.
Kieninger, Ann-Katrin
Khataokar, Atul
O’Hara, Brendan J.
Behrmann, Lara V.
Neiditch, Matthew B.
Benning, Christoph
Waters, Christopher M.
Ng, Wai-Leung
author_facet Severin, Geoffrey B.
Ramliden, Miriam S.
Hawver, Lisa A.
Wang, Kun
Pell, Macy E.
Kieninger, Ann-Katrin
Khataokar, Atul
O’Hara, Brendan J.
Behrmann, Lara V.
Neiditch, Matthew B.
Benning, Christoph
Waters, Christopher M.
Ng, Wai-Leung
author_sort Severin, Geoffrey B.
collection PubMed
description Sensing and responding to environmental changes is essential for bacteria to adapt and thrive, and nucleotide-derived second messengers are central signaling systems in this process. The most recently identified bacterial cyclic dinucleotide second messenger, 3′, 3′-cyclic GMP-AMP (cGAMP), was first discovered in the El Tor biotype of Vibrio cholerae. The cGAMP synthase, DncV, is encoded on the VSP-1 pathogenicity island, which is found in all El Tor isolates that are responsible for the current seventh pandemic of cholera but not in the classical biotype. We determined that unregulated production of DncV inhibits growth in El Tor V. cholerae but has no effect on the classical biotype. This cGAMP-dependent phenotype can be suppressed by null mutations in vc0178 immediately 5′ of dncV in VSP-1. VC0178 [renamed as cGAMP-activated phospholipase in Vibrio (CapV)] is predicted to be a patatin-like phospholipase, and coexpression of capV and dncV is sufficient to induce growth inhibition in classical V. cholerae and Escherichia coli. Furthermore, cGAMP binds to CapV and directly activates its hydrolase activity in vitro. CapV activated by cGAMP in vivo degrades phospholipids in the cell membrane, releasing 16:1 and 18:1 free fatty acids. Together, we demonstrate that cGAMP activates CapV phospholipase activity to target the cell membrane and suggest that acquisition of this second messenger signaling pathway may contribute to the emergence of the El Tor biotype as the etiological agent behind the seventh cholera pandemic.
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spelling pubmed-60420762018-07-13 Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae Severin, Geoffrey B. Ramliden, Miriam S. Hawver, Lisa A. Wang, Kun Pell, Macy E. Kieninger, Ann-Katrin Khataokar, Atul O’Hara, Brendan J. Behrmann, Lara V. Neiditch, Matthew B. Benning, Christoph Waters, Christopher M. Ng, Wai-Leung Proc Natl Acad Sci U S A PNAS Plus Sensing and responding to environmental changes is essential for bacteria to adapt and thrive, and nucleotide-derived second messengers are central signaling systems in this process. The most recently identified bacterial cyclic dinucleotide second messenger, 3′, 3′-cyclic GMP-AMP (cGAMP), was first discovered in the El Tor biotype of Vibrio cholerae. The cGAMP synthase, DncV, is encoded on the VSP-1 pathogenicity island, which is found in all El Tor isolates that are responsible for the current seventh pandemic of cholera but not in the classical biotype. We determined that unregulated production of DncV inhibits growth in El Tor V. cholerae but has no effect on the classical biotype. This cGAMP-dependent phenotype can be suppressed by null mutations in vc0178 immediately 5′ of dncV in VSP-1. VC0178 [renamed as cGAMP-activated phospholipase in Vibrio (CapV)] is predicted to be a patatin-like phospholipase, and coexpression of capV and dncV is sufficient to induce growth inhibition in classical V. cholerae and Escherichia coli. Furthermore, cGAMP binds to CapV and directly activates its hydrolase activity in vitro. CapV activated by cGAMP in vivo degrades phospholipids in the cell membrane, releasing 16:1 and 18:1 free fatty acids. Together, we demonstrate that cGAMP activates CapV phospholipase activity to target the cell membrane and suggest that acquisition of this second messenger signaling pathway may contribute to the emergence of the El Tor biotype as the etiological agent behind the seventh cholera pandemic. National Academy of Sciences 2018-06-26 2018-06-11 /pmc/articles/PMC6042076/ /pubmed/29891656 http://dx.doi.org/10.1073/pnas.1801233115 Text en Copyright © 2018 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Severin, Geoffrey B.
Ramliden, Miriam S.
Hawver, Lisa A.
Wang, Kun
Pell, Macy E.
Kieninger, Ann-Katrin
Khataokar, Atul
O’Hara, Brendan J.
Behrmann, Lara V.
Neiditch, Matthew B.
Benning, Christoph
Waters, Christopher M.
Ng, Wai-Leung
Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae
title Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae
title_full Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae
title_fullStr Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae
title_full_unstemmed Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae
title_short Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae
title_sort direct activation of a phospholipase by cyclic gmp-amp in el tor vibrio cholerae
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6042076/
https://www.ncbi.nlm.nih.gov/pubmed/29891656
http://dx.doi.org/10.1073/pnas.1801233115
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