Bacterial cell cycle control by citrate synthase independent of enzymatic activity
- University of Geneva, Switzerland
Abstract
Proliferating cells must coordinate central metabolism with the cell cycle. How central energy metabolism regulates bacterial cell cycle functions is not well understood. Our forward genetic selection unearthed the Krebs cycle enzyme citrate synthase (CitA) as a checkpoint regulator controlling the G1→S transition in the polarized alpha-proteobacterium Caulobacter crescentus, a model for cell cycle regulation and asymmetric cell division. We find that loss of CitA promotes the accumulation of active CtrA, an essential cell cycle transcriptional regulator that maintains cells in G1-phase, provided that the (p)ppGpp alarmone is present. The enzymatic activity of CitA is dispensable for CtrA control and functional citrate synthase paralogs cannot replace CitA in promoting S-phase entry. Our evidence suggests that CitA was appropriated specifically to function as a moonlighting enzyme to link central energy metabolism with S-phase entry. Control of the G1-phase with a central metabolic enzyme may be a common mechanism of cellular regulation.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Tn-seq and metabolomics data.
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Polymerase occupancy (ChIP-Seq) in WT and mutants of Caulobacter crescentus NA1000NCBI Gene Expression Omnibus, GSE144533.
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Examination of 5 transcripton factor binding in two different speciesNCBI Gene Expression Omnibus, GSE52849.
Article and author information
Author details
Patrick H Viollier
Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (31003A_182576)
- Patrick H Viollier
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Bergé et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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