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:

Severin, Geoffrey B.; Ramliden, Miriam S.; Hawver, Lisa A.; Wang, Kun ;

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• Search DOE PAGES for ORCID "0000-0003-1715-990X"
• Search orcid.org for ORCID "0000-0003-1715-990X"

Pell, Macy E.; Kieninger, Ann-Katrin; Khataokar, Atul; O’Hara, Brendan J.; Behrmann, Lara V.; Neiditch, Matthew B.; Benning, Christoph ;

• Search DOE PAGES for author "Benning, Christoph"
• Search DOE PAGES for ORCID "0000-0001-8585-3667"
• Search orcid.org for ORCID "0000-0001-8585-3667"

Waters, Christopher M.; Ng, Wai-Leung

• Search DOE PAGES for author "Ng, Wai-Leung"
• Search DOE PAGES for ORCID "0000-0002-8966-6604"
• Search orcid.org for ORCID "0000-0002-8966-6604"

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) (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