PMID- 31015332 OWN - NLM STAT- MEDLINE DCOM- 20190620 LR - 20200514 IS - 2150-7511 (Electronic) VI - 10 IP - 2 DP - 2019 Apr 23 TI - Functional Specialization in Vibrio cholerae Diguanylate Cyclases: Distinct Modes of Motility Suppression and c-di-GMP Production. LID - 10.1128/mBio.00670-19 [doi] LID - e00670-19 AB - Vibrio cholerae biofilm formation and associated motility suppression are correlated with increased concentrations of cyclic diguanylate monophosphate (c-di-GMP), which are in turn driven by increased levels and/or activity of diguanylate cyclases (DGCs). To further our understanding of how c-di-GMP modulators in V. cholerae individually and collectively influence motility with cellular resolution, we determined how DGCs CdgD and CdgH impact intracellular c-di-GMP levels, motility, and biofilm formation. Our results indicated that CdgH strongly influences swim speed distributions; cells in which cdgH was deleted had higher average swim speeds than wild-type cells. Furthermore, our results suggest that CdgD, rather than CdgH, is the dominant DGC responsible for postattachment c-di-GMP production in biofilms. Lipopolysaccharide (LPS) biosynthesis genes were found to be extragenic bypass suppressors of the motility phenotypes of strains DeltacdgD and DeltacdgH We compared the motility regulation mechanism of the DGCs with that of Gmd, an LPS O-antigen biosynthesis protein, and discovered that comodulation of c-di-GMP levels by these motility effectors can be positively or negatively cooperative rather than simply additive. Taken together, these results suggest that different environmental and metabolic inputs orchestrate DGC responses of V. cholerae via c-di-GMP production and motility modulation.IMPORTANCE Cyclic diguanylate monophosphate (c-di-GMP) is a broadly conserved bacterial signaling molecule that affects motility, biofilm formation, and virulence. Although it has been known that high intracellular concentrations of c-di-GMP correlate with motility suppression and biofilm formation, how the 53 predicted c-di-GMP modulators in Vibrio cholerae collectively influence motility is not understood in detail. Here we used a combination of plate assays and single-cell tracking methods to correlate motility and biofilm formation outcomes with specific enzymes involved in c-di-GMP synthesis in Vibrio cholerae, the causative agent of the disease cholera. CI - Copyright (c) 2019 Zamorano-Sanchez et al. FAU - Zamorano-Sanchez, David AU - Zamorano-Sanchez D AD - Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA. FAU - Xian, Wujing AU - Xian W AD - Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA. FAU - Lee, Calvin K AU - Lee CK AD - Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA. FAU - Salinas, Mauro AU - Salinas M AD - Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA. FAU - Thongsomboon, Wiriya AU - Thongsomboon W AD - Department of Chemistry, Stanford University, Stanford, California, USA. FAU - Cegelski, Lynette AU - Cegelski L AD - Department of Chemistry, Stanford University, Stanford, California, USA. FAU - Wong, Gerard C L AU - Wong GCL AD - Department of Bioengineering, University of California, Los Angeles, Los Angeles, California, USA gclwong.ucla@gmail.com fyildiz@ucsc.edu. AD - Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, California, USA. AD - California Nano Systems Institute, University of California, Los Angeles, Los Angeles, California, USA. FAU - Yildiz, Fitnat H AU - Yildiz FH AD - Department of Microbiology and Environmental Toxicology, University of California, Santa Cruz, Santa Cruz, California, USA gclwong.ucla@gmail.com fyildiz@ucsc.edu. LA - eng GR - R01 AI102584/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20190423 PL - United States TA - mBio JT - mBio JID - 101519231 RN - 0 (Escherichia coli Proteins) RN - 61093-23-0 (bis(3',5')-cyclic diguanylic acid) RN - EC 4.6.- (Phosphorus-Oxygen Lyases) RN - EC 4.6.1.- (diguanylate cyclase) RN - H2D2X058MU (Cyclic GMP) SB - IM EIN - mBio. 2020 Sep 22;11(5):. PMID: 32963008 MH - Biofilms/*growth & development MH - Cyclic GMP/*analogs & derivatives/metabolism MH - Escherichia coli Proteins/genetics/*metabolism MH - Gene Deletion MH - Gene Expression Regulation, Bacterial MH - Locomotion MH - Phosphorus-Oxygen Lyases/genetics/*metabolism MH - Vibrio cholerae/*enzymology/genetics/*physiology PMC - PMC6479008 OTO - NOTNLM OT - Vibrio cholerae OT - biofilm OT - c-di-GMP OT - motility EDAT- 2019/04/25 06:00 MHDA- 2019/06/21 06:00 PMCR- 2019/04/23 CRDT- 2019/04/25 06:00 PHST- 2019/04/25 06:00 [entrez] PHST- 2019/04/25 06:00 [pubmed] PHST- 2019/06/21 06:00 [medline] PHST- 2019/04/23 00:00 [pmc-release] AID - mBio.00670-19 [pii] AID - mBio00670-19 [pii] AID - 10.1128/mBio.00670-19 [doi] PST - epublish SO - mBio. 2019 Apr 23;10(2):e00670-19. doi: 10.1128/mBio.00670-19.