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Microbiology. 2015 Mar;161(Pt 3):553-64. doi: 10.1099/mic.0.000032. Epub 2015 Jan 8.

(p)ppGpp modulates cell size and the initiation of DNA replication in Caulobacter crescentus in response to a block in lipid biosynthesis.

Author information

1
Department of Biology, Center for Cancer and Developmental Biology, Interdisciplinary Research Institute for the Sciences, California State University Northridge, Northridge, CA 91330-8303, USA.
2
Department of Chemistry, Williams College, Williamstown, MA 01267, USA.
3
Department of Biological Sciences, California State University Fullerton, Fullerton, CA 92831, USA Mental Health Research Institute, Melbourne Brain Centre, Parkville, Victoria 3052, Australia.
4
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.

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.

PMID:
25573769
PMCID:
PMC4339654
DOI:
10.1099/mic.0.000032
[Indexed for MEDLINE]
Free PMC Article

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