title: A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.
abstract: Generally, the second messenger bis-(3'-5')-cyclic dimeric GMP (c-di-GMP) regulates the switch between motile and sessile lifestyles in bacteria. Here, we show that c-di-GMP is an essential regulator of multicellular development in the social bacterium Myxococcus xanthus. In response to starvation, M. xanthus initiates a developmental program that culminates in formation of spore-filled fruiting bodies. We show that c-di-GMP accumulates at elevated levels during development and that this increase is essential for completion of development whereas excess c-di-GMP does not interfere with development. MXAN3735 (renamed DmxB) is identified as a diguanylate cyclase that only functions during development and is responsible for this increased c-di-GMP accumulation. DmxB synthesis is induced in response to starvation, thereby restricting DmxB activity to development. DmxB is essential for development and functions downstream of the Dif chemosensory system to stimulate exopolysaccharide accumulation by inducing transcription of a subset of the genes encoding proteins involved in exopolysaccharide synthesis. The developmental defects in the dmxB mutant are non-cell autonomous and rescued by co-development with a strain proficient in exopolysaccharide synthesis, suggesting reduced exopolysaccharide accumulation as the causative defect in this mutant. The NtrC-like transcriptional regulator EpsI/Nla24, which is required for exopolysaccharide accumulation, is identified as a c-di-GMP receptor, and thus a putative target for DmxB generated c-di-GMP. Because DmxB can be-at least partially-functionally replaced by a heterologous diguanylate cyclase, these results altogether suggest a model in which a minimum threshold level of c-di-GMP is essential for the successful completion of multicellular development in M. xanthus.
authors.affiliation: Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
authors.forename: Dorota
authors.initials: D
authors.lastname: Skotnicka
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California - Davis, Davis, California, United States of America.
authors.forename: Gregory T
authors.identifier: 0000-0001-5817-241X
authors.initials: GT
authors.lastname: Smaldone
authors.affiliation: Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Petters
authors.affiliation: Molecular Microbiology Department, John Innes Centre, Norwich, United Kingdom.
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Trampari
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California - Davis, Davis, California, United States of America.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Liang
authors.affiliation: Research Core Unit Metabolomics, Hannover Medical School, Hannover, Germany.
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.affiliation: Molecular Microbiology Department, John Innes Centre, Norwich, United Kingdom.|School of Biological Sciences, University of East Anglia, Norwich, United Kingdom.
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Malone
authors.affiliation: Department of Microbiology and Molecular Genetics, University of California - Davis, Davis, California, United States of America.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Singer
authors.affiliation: Department of Ecophysiology, Max Planck Institute for Terrestrial Microbiology, Marburg, Germany.
authors.forename: Lotte
authors.initials: L
authors.lastname: Søgaard-Andersen
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics*; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D016941:Myxococcus xanthus / Q000235:genetics* / Q000254:growth & development; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics*; D013171:Spores, Bacterial / Q000235:genetics* / Q000254:growth & development; D013217:Starvation
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP