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

Abstract

Sensing and responding to environmental changes is critical 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 TorV. choleraebut has no effect on the classical biotype. This cGAMP-dependent phenotype can be suppressed by null mutations invc0178immediately 5' ofdncVin VSP-1. VC0178 [renamed as cGAMP-activated phospholipase in Vibrio (CapV)] is predicted to be a patatin-like phospholipase, and coexpression of capVand dncVis sufficient to induce growth inhibition in classicalV. choleraeandEscherichia 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 imply that acquisition of this second messengermore » signaling pathway may contribute to the emergence of the El Tor biotype as the etiological agent behind the seventh cholera pandemic.« less

Authors:

Severin, Geoffrey B. ^[1]; Ramliden, Miriam S. ^[2]; Hawver, Lisa A. ^[3]; Wang, Kun  ^[4];

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• Search DOE PAGES for ORCID "0000-0003-1715-990X"
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Pell, Macy E. ^[5]; Kieninger, Ann-Katrin ^[5]; Khataokar, Atul ^[6]; O’Hara, Brendan J. ^[2]; Behrmann, Lara V. ^[5]; Neiditch, Matthew B. ^[6]; Benning, Christoph  ^[4];

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Waters, Christopher M. ^[5]; Ng, Wai-Leung  ^[2]

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• Search DOE PAGES for ORCID "0000-0002-8966-6604"
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+ Show Author Affiliations

1. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824,
2. Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111,, Graduate Program in Molecular Microbiology, Tufts Sackler School of Biomedical Sciences, Boston, MA 02111,
3. Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111,
4. Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824,, Michigan State University–Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824,
5. Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824,
6. Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103

Publication Date:

2018-06-11

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); 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