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

Abstract

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 activitymore » 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.« less

Authors:
; ; ; ORCiD logo; ; ; ; ; ; ; ORCiD logo; ; ORCiD logo
Publication Date:
Research Org.:
Michigan State Univ., East Lansing, MI (United States). MSU-DOE Plant Research Laboratory
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH)
OSTI Identifier:
1441128
Alternate Identifier(s):
OSTI ID: 1547352
Grant/Contract Number:  
FG02-98ER20305; FG02-91ER20021
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 115 Journal Issue: 26; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; second messengers; cyclic dinucleotides; phospholipid metabolism; pathogenicity island; cGAMP

Citation Formats

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., and Ng, Wai-Leung. Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae. United States: N. p., 2018. Web. doi:10.1073/pnas.1801233115.
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. United States. doi:10.1073/pnas.1801233115.
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., and Ng, Wai-Leung. Mon . "Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae". United States. doi:10.1073/pnas.1801233115.
@article{osti_1441128,
title = {Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae},
author = {Severin, Geoffrey B. and Ramliden, Miriam S. and Hawver, Lisa A. and Wang, Kun and Pell, Macy E. and Kieninger, Ann-Katrin and Khataokar, Atul and O’Hara, Brendan J. and Behrmann, Lara V. and Neiditch, Matthew B. and Benning, Christoph and Waters, Christopher M. and Ng, Wai-Leung},
abstractNote = {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.},
doi = {10.1073/pnas.1801233115},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 26,
volume = 115,
place = {United States},
year = {2018},
month = {6}
}

Journal Article:
Free Publicly Available Full Text
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DOI: 10.1073/pnas.1801233115

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Works referenced in this record:

Control of bacterial exoelectrogenesis by c-AMP-GMP
journal, April 2015

  • Nelson, James W.; Sudarsan, Narasimhan; Phillips, Grace E.
  • Proceedings of the National Academy of Sciences, Vol. 112, Issue 17
  • DOI: 10.1073/pnas.1419264112

Recent functional insights into the role of (p)ppGpp in bacterial physiology
journal, April 2015

  • Hauryliuk, Vasili; Atkinson, Gemma C.; Murakami, Katsuhiko S.
  • Nature Reviews Microbiology, Vol. 13, Issue 5
  • DOI: 10.1038/nrmicro3448

Exploring Environmental Control of Cyclic di-GMP Signaling in Vibrio cholerae by Using the Ex Vivo Lysate Cyclic di-GMP Assay (TELCA)
journal, June 2013

  • Koestler, Benjamin J.; Waters, Christopher M.
  • Applied and Environmental Microbiology, Vol. 79, Issue 17
  • DOI: 10.1128/AEM.01596-13

c-di-AMP Is a New Second Messenger in Staphylococcus aureus with a Role in Controlling Cell Size and Envelope Stress
journal, September 2011


Systematic identification of conserved bacterial c-di-AMP receptor proteins
journal, May 2013

  • Corrigan, R. M.; Campeotto, I.; Jeganathan, T.
  • Proceedings of the National Academy of Sciences, Vol. 110, Issue 22
  • DOI: 10.1073/pnas.1300595110

Control of fatty acid desaturation: a mechanism conserved from bacteria to humans
journal, December 2006


Positive selection vectors for allelic exchange
journal, February 1996


Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway
journal, December 2012


Mechanism for Inhibition of Vibrio cholerae ToxT Activity by the Unsaturated Fatty Acid Components of Bile
journal, March 2015

  • Plecha, Sarah C.; Withey, Jeffrey H.
  • Journal of Bacteriology, Vol. 197, Issue 10
  • DOI: 10.1128/JB.02409-14

N-terminal Residues of the Vibrio cholerae Virulence Regulatory Protein ToxT Involved in Dimerization and Modulation by Fatty Acids
journal, June 2011

  • Childers, Brandon M.; Cao, Xiaohang; Weber, Gregor G.
  • Journal of Biological Chemistry, Vol. 286, Issue 32
  • DOI: 10.1074/jbc.M111.258780

<em>Arabidopsis thaliana</em> Polar Glycerolipid Profiling by Thin Layer Chromatography (TLC) Coupled with Gas-Liquid Chromatography (GLC)
journal, January 2011

  • Wang, Zhen; Benning, Christoph
  • Journal of Visualized Experiments, Issue 49
  • DOI: 10.3791/2518

Integration of Cyclic di-GMP and Quorum Sensing in the Control of vpsT and aphA in Vibrio cholerae
journal, September 2011

  • Srivastava, Disha; Harris, Rebecca C.; Waters, Christopher M.
  • Journal of Bacteriology, Vol. 193, Issue 22
  • DOI: 10.1128/JB.05167-11

Bacterial Signal Transduction by Cyclic Di-GMP and Other Nucleotide Second Messengers
journal, June 2015

  • Hengge, Regine; Gründling, Angelika; Jenal, Urs
  • Journal of Bacteriology, Vol. 198, Issue 1
  • DOI: 10.1128/JB.00331-15

Cyclic AMP in prokaryotes.
journal, January 1992


Visualization of membrane domains in Escherichia coli
journal, June 1999


Two Compounds implicated in the Function of the RC Gene of Escherichia coli
journal, March 1969

  • Cashel, Michael; Gallant, Jonathan
  • Nature, Vol. 221, Issue 5183
  • DOI: 10.1038/221838a0

Homeoviscous Adaptation and the Regulation of Membrane Lipids
journal, December 2016

  • Ernst, Robert; Ejsing, Christer S.; Antonny, Bruno
  • Journal of Molecular Biology, Vol. 428, Issue 24
  • DOI: 10.1016/j.jmb.2016.08.013

Structural Biochemistry of a Bacterial Checkpoint Protein Reveals Diadenylate Cyclase Activity Regulated by DNA Recombination Intermediates
journal, April 2008


Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
journal, December 2012


Dimeric c-di-GMP Is Required for Post-translational Regulation of Alginate Production in Pseudomonas aeruginosa
journal, March 2015

  • Whitney, John C.; Whitfield, Gregory B.; Marmont, Lindsey S.
  • Journal of Biological Chemistry, Vol. 290, Issue 20
  • DOI: 10.1074/jbc.M115.645051

Synthesis of Guanosine Tetra- and Pentaphosphate Requires the Presence of a Codon-Specific, Uncharged Transfer Ribonucleic Acid in the Acceptor Site of Ribosomes
journal, May 1973

  • Haseltine, W. A.; Block, R.
  • Proceedings of the National Academy of Sciences, Vol. 70, Issue 5, p. 1564-1568
  • DOI: 10.1073/pnas.70.5.1564

Structural Basis for Molecular Discrimination by a 3′,3′-cGAMP Sensing Riboswitch
journal, April 2015


A vital stain for studying membrane dynamics in bacteria: a novel mechanism controlling septation during Bacillus subtilis sporulation
journal, February 1999


Cyclic GMP–AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA
journal, June 2017


Identification of FleQ from Pseudomonas aeruginosa as a c-di-GMP-responsive transcription factor
journal, July 2008


c-di-AMP Secreted by Intracellular Listeria monocytogenes Activates a Host Type I Interferon Response
journal, May 2010


Activity-based protein profiling: The serine hydrolases
journal, December 1999

  • Liu, Y.; Patricelli, M. P.; Cravatt, B. F.
  • Proceedings of the National Academy of Sciences, Vol. 96, Issue 26
  • DOI: 10.1073/pnas.96.26.14694

Structure-Guided Reprogramming of Human cGAS Dinucleotide Linkage Specificity
journal, August 2014


A Plastid Phosphatidylglycerol Lipase Contributes to the Export of Acyl Groups from Plastids for Seed Oil Biosynthesis
journal, July 2017

  • Wang, Kun; Froehlich, John E.; Zienkiewicz, Agnieszka
  • The Plant Cell, Vol. 29, Issue 7
  • DOI: 10.1105/tpc.17.00397

Cyclic di-GMP: the First 25 Years of a Universal Bacterial Second Messenger
journal, March 2013

  • Romling, U.; Galperin, M. Y.; Gomelsky, M.
  • Microbiology and Molecular Biology Reviews, Vol. 77, Issue 1
  • DOI: 10.1128/MMBR.00043-12

Cyclic AMP and cell division in Escherichia coli.
journal, January 1988


Comparative genomic analyses reveal a vast, novel network of nucleotide-centric systems in biological conflicts, immunity and signaling
journal, November 2015

  • Burroughs, A. Maxwell; Zhang, Dapeng; Schäffer, Daniel E.
  • Nucleic Acids Research, Vol. 43, Issue 22
  • DOI: 10.1093/nar/gkv1267

Structural and Functional Analysis of the CspB Protease Required for Clostridium Spore Germination
journal, February 2013


Comparative genomic analysis of Vibrio cholerae: Genes that correlate with cholera endemic and pandemic disease
journal, January 2002

  • Dziejman, M.; Balon, E.; Boyd, D.
  • Proceedings of the National Academy of Sciences, Vol. 99, Issue 3
  • DOI: 10.1073/pnas.042667999

Profiling Serine Hydrolase Activities in Complex Proteomes
journal, April 2001

  • Kidd, Dana; Liu, Yongsheng; Cravatt, Benjamin F.
  • Biochemistry, Vol. 40, Issue 13
  • DOI: 10.1021/bi002579j

Hybrid promiscuous (Hypr) GGDEF enzymes produce cyclic AMP-GMP (3′, 3′-cGAMP)
journal, February 2016

  • Hallberg, Zachary F.; Wang, Xin C.; Wright, Todd A.
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 7
  • DOI: 10.1073/pnas.1515287113

DarR, a TetR-like Transcriptional Factor, Is a Cyclic Di-AMP-responsive Repressor in Mycobacterium smegmatis
journal, December 2012

  • Zhang, Lei; Li, Weihui; He, Zheng-Guo
  • Journal of Biological Chemistry, Vol. 288, Issue 5
  • DOI: 10.1074/jbc.M112.428110

Identification and characterization of phosphodiesterases that specifically degrade 3′3′-cyclic GMP-AMP
journal, April 2015

  • Gao, Juyi; Tao, Jianli; Liang, Weili
  • Cell Research, Vol. 25, Issue 5
  • DOI: 10.1038/cr.2015.40

Structure of Vibrio cholerae ToxT reveals a mechanism for fatty acid regulation of virulence genes
journal, February 2010

  • Lowden, M. J.; Skorupski, K.; Pellegrini, M.
  • Proceedings of the National Academy of Sciences, Vol. 107, Issue 7
  • DOI: 10.1073/pnas.0915021107

Seroepidemiologic Studies during a Simultaneous Epidemic of Infection with El Tor Ogawa and Classical Inaba Vibrio cholerae
journal, May 1970


Temperature Sensing by Membranes
journal, September 2014


Origins of the current seventh cholera pandemic
journal, November 2016

  • Hu, Dalong; Liu, Bin; Feng, Lu
  • Proceedings of the National Academy of Sciences, Vol. 113, Issue 48
  • DOI: 10.1073/pnas.1608732113

c-di-AMP reports DNA integrity during sporulation in Bacillus subtilis
journal, May 2011

  • Oppenheimer-Shaanan, Yaara; Wexselblatt, Ezequiel; Katzhendler, Jehoshua
  • EMBO reports, Vol. 12, Issue 6
  • DOI: 10.1038/embor.2011.77

Essential Role for Cyclic AMP and Its Receptor Protein in Yersinia enterocolitica Virulence
journal, July 2002


Interplay between Cyclic AMP-Cyclic AMP Receptor Protein and Cyclic di-GMP Signaling in Vibrio cholerae Biofilm Formation
journal, August 2008

  • Fong, J. C. N.; Yildiz, F. H.
  • Journal of Bacteriology, Vol. 190, Issue 20
  • DOI: 10.1128/JB.00466-08

Coordinated Regulation of Accessory Genetic Elements Produces Cyclic Di-Nucleotides for V. cholerae Virulence
journal, April 2012


Control of potassium homeostasis is an essential function of the second messenger cyclic di-AMP in Bacillus subtilis
journal, April 2017


Diversity in (p)ppGpp metabolism and effectors
journal, April 2015


The expanding superfamily of phospholipase A2 enzymes: classification and characterization
journal, October 2000

  • Six, David A.; Dennis, Edward A.
  • Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Vol. 1488, Issue 1-2
  • DOI: 10.1016/S1388-1981(00)00105-0