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DOI10.1073/pnas.1801233115
Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae
Severin G.B.; Ramliden M.S.; Hawver L.A.; Wang K.; Pell M.E.; Kieninger A.-K.; Khataokar A.; O’Hara B.J.; Behrmann L.V.; Neiditch M.B.; Benning C.; Waters C.M.; Ng W.-L.
发表日期2018
ISSN0027-8424
起始页码E6048
结束页码E6055
卷号115期号:26
英文摘要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. © 2018 National Academy of Sciences. All Rights Reserved.
英文关键词CGAMP; Cyclic dinucleotides; Patho enicit island; Phospholipid metabolism; Second messengers
语种英语
scopus关键词3',3' cyclic GMP AMP; CapV phospholipase; cyclic AMP; cyclic GMP; DncV protein; phosphatidylethanolamine; phosphatidylglycerol; phospholipase; synthetase; unclassified drug; bacterial protein; cyclic guanosine monophosphate-adenosine monophosphate; cyclic nucleotide; phospholipase; Article; bacterial gene; bacterial growth; capV gene; cell membrane; controlled study; dncV gene; ectopic expression; Escherichia coli; gene mutation; growth inhibition; nonhuman; pathogenicity island; priority journal; second messenger; Vibrio cholerae; enzymology; genetics; metabolism; physiology; Vibrio cholerae; Bacterial Proteins; Cell Membrane; Nucleotides, Cyclic; Phospholipases; Second Messenger Systems; Vibrio cholerae
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/160502
作者单位Severin, G.B., Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, United States; Ramliden, M.S., Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, United States, Graduate Program in Molecular Microbiology, Tufts Sackler School of Biomedical Sciences, Boston, MA 02111, United States; Hawver, L.A., Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, United States; Wang, K., Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, United States, Michigan State University, Department of Energy Plant Research Laboratory, Michigan State University, East Lansing, MI 48824, United States; Pell, M.E., Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI 48824, United States; Kieninger, A.-K., Department of Microbiology and Molecular Genetics, Michigan State University...
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Severin G.B.,Ramliden M.S.,Hawver L.A.,et al. Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae[J],2018,115(26).
APA Severin G.B..,Ramliden M.S..,Hawver L.A..,Wang K..,Pell M.E..,...&Ng W.-L..(2018).Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae.Proceedings of the National Academy of Sciences of the United States of America,115(26).
MLA Severin G.B.,et al."Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae".Proceedings of the National Academy of Sciences of the United States of America 115.26(2018).
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