title: Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT.
abstract: Two chemical signaling systems, quorum sensing (QS) and 3',5'-cyclic diguanylic acid (c-di-GMP), reciprocally control biofilm formation in Vibrio cholerae. QS is the process by which bacteria communicate via the secretion and detection of autoinducers, and in V. cholerae, QS represses biofilm formation. c-di-GMP is an intracellular second messenger that contains information regarding local environmental conditions, and in V. cholerae, c-di-GMP activates biofilm formation. Here we show that HapR, a major regulator of QS, represses biofilm formation in V. cholerae through two distinct mechanisms. HapR controls the transcription of 14 genes encoding a group of proteins that synthesize and degrade c-di-GMP. The net effect of this transcriptional program is a reduction in cellular c-di-GMP levels at high cell density and, consequently, a decrease in biofilm formation. Increasing the c-di-GMP concentration at high cell density to the level present in the low-cell-density QS state restores biofilm formation, showing that c-di-GMP is epistatic to QS in the control of biofilm formation in V. cholerae. In addition, HapR binds to and directly represses the expression of the biofilm transcriptional activator, vpsT. Together, our results suggest that V. cholerae integrates information about the vicinal bacterial community contained in extracellular QS autoinducers with the intracellular environmental information encoded in c-di-GMP to control biofilm formation.
authors.affiliation: Department of Molecular Biology, Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Waters
authors.forename: Wenyun
authors.initials: W
authors.lastname: Lu
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Bassler
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018441:Biofilms / Q000254:growth & development*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005434:Flow Cytometry; D015964:Gene Expression Regulation, Bacterial; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D053038:Quorum Sensing / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015534:Trans-Activators; D049452:Green Fluorescent Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP