A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.

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 st...

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Main Authors: Dorota Skotnicka, Gregory T Smaldone, Tobias Petters, Eleftheria Trampari, Jennifer Liang, Volkhard Kaever, Jacob G Malone, Mitchell Singer, Lotte Søgaard-Andersen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-05-01
Series:PLoS Genetics
Online Access:https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006080&type=printable
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author Dorota Skotnicka
Gregory T Smaldone
Tobias Petters
Eleftheria Trampari
Jennifer Liang
Volkhard Kaever
Jacob G Malone
Mitchell Singer
Lotte Søgaard-Andersen
author_facet Dorota Skotnicka
Gregory T Smaldone
Tobias Petters
Eleftheria Trampari
Jennifer Liang
Volkhard Kaever
Jacob G Malone
Mitchell Singer
Lotte Søgaard-Andersen
author_sort Dorota Skotnicka
collection DOAJ
description 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.
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spelling doaj-art-f4d42ca4bffe41359df19cf1b47b1ed52025-08-20T03:11:10ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042016-05-01125e100608010.1371/journal.pgen.1006080A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.Dorota SkotnickaGregory T SmaldoneTobias PettersEleftheria TrampariJennifer LiangVolkhard KaeverJacob G MaloneMitchell SingerLotte Søgaard-AndersenGenerally, 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.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006080&type=printable
spellingShingle Dorota Skotnicka
Gregory T Smaldone
Tobias Petters
Eleftheria Trampari
Jennifer Liang
Volkhard Kaever
Jacob G Malone
Mitchell Singer
Lotte Søgaard-Andersen
A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.
PLoS Genetics
title A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.
title_full A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.
title_fullStr A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.
title_full_unstemmed A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.
title_short A Minimal Threshold of c-di-GMP Is Essential for Fruiting Body Formation and Sporulation in Myxococcus xanthus.
title_sort minimal threshold of c di gmp is essential for fruiting body formation and sporulation in myxococcus xanthus
url https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1006080&type=printable
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