title: (p)ppGpp modulates cell size and the initiation of DNA replication in Caulobacter crescentus in response to a block in lipid biosynthesis.
abstract: Stress conditions, such as a block in fatty acid synthesis, signal bacterial cells to exit the cell cycle. Caulobacter crescentus FabH is a cell-cycle-regulated β-ketoacyl-acyl carrier protein synthase that initiates lipid biosynthesis and is essential for growth in rich media. To explore how C. crescentus responds to a block in lipid biosynthesis, we created a FabH-depletion strain. We found that FabH depletion blocks lipid biosynthesis in rich media and causes a cell cycle arrest that requires the alarmone (p)ppGpp for adaptation. Notably, basal levels of (p)ppGpp coordinate both a reduction in cell volume and a block in the over-initiation of DNA replication in response to FabH depletion. The gene ctrA encodes a master transcription factor that directly regulates 95 cell-cycle-controlled genes while also functioning to inhibit the initiation of DNA replication. Here, we demonstrate that ctrA transcription is (p)ppGpp-dependent during fatty acid starvation. CtrA fails to accumulate when FabH is depleted in the absence of (p)ppGpp due to a substantial reduction in ctrA transcription. The (p)ppGpp-dependent maintenance of ctrA transcription during fatty acid starvation initiated from only one of the two ctrA promoters. In the absence of (p)ppGpp, the majority of FabH-depleted cells enter a viable but non-culturable state, with multiple chromosomes, and are unable to recover from the miscoordination of cell cycle events. Thus, basal levels of (p)ppGpp facilitate C. crescentus' re-entry into the cell cycle after termination of fatty acid starvation.
authors.affiliation: Department of Biology, Center for Cancer and Developmental Biology, Interdisciplinary Research Institute for the Sciences, California State University Northridge, Northridge, CA 91330-8303, USA.
authors.forename: Kristina V
authors.initials: KV
authors.lastname: Stott
authors.affiliation: Department of Biology, Center for Cancer and Developmental Biology, Interdisciplinary Research Institute for the Sciences, California State University Northridge, Northridge, CA 91330-8303, USA.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Wood
authors.affiliation: Department of Chemistry, Williams College, Williamstown, MA 01267, USA.
authors.forename: Jimmy A
authors.initials: JA
authors.lastname: Blair
authors.affiliation: Department of Biology, Center for Cancer and Developmental Biology, Interdisciplinary Research Institute for the Sciences, California State University Northridge, Northridge, CA 91330-8303, USA.
authors.forename: Bao T
authors.initials: BT
authors.lastname: Nguyen
authors.affiliation: Department of Biology, Center for Cancer and Developmental Biology, Interdisciplinary Research Institute for the Sciences, California State University Northridge, Northridge, CA 91330-8303, USA.
authors.forename: Anabel
authors.initials: A
authors.lastname: Herrera
authors.affiliation: Department of Biology, Center for Cancer and Developmental Biology, Interdisciplinary Research Institute for the Sciences, California State University Northridge, Northridge, CA 91330-8303, USA.
authors.forename: Yannet G Perez
authors.initials: YG
authors.lastname: Mora
authors.affiliation: Department of Biological Sciences, California State University Fullerton, Fullerton, CA 92831, USA Mental Health Research Institute, Melbourne Brain Centre, Parkville, Victoria 3052, Australia.
authors.forename: Math P
authors.initials: MP
authors.lastname: Cuajungco
authors.affiliation: Department of Biology, Center for Cancer and Developmental Biology, Interdisciplinary Research Institute for the Sciences, California State University Northridge, Northridge, CA 91330-8303, USA sean.murray@csun.edu.
authors.forename: Sean R
authors.initials: SR
authors.lastname: Murray
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016935:Caulobacter crescentus / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication; D015964:Gene Expression Regulation, Bacterial; D006150:Guanine Nucleotides / Q000378:metabolism*; D008055:Lipids / Q000096:biosynthesis*
chemical_list: D001426:Bacterial Proteins; D006150:Guanine Nucleotides; D008055:Lipids; C018957:guanosine 5'-diphosphate-3'-monophosphate