Bacterial cell cycle control by citrate synthase independent of enzymatic activity.

ELife
Matthieu BergéPatrick H VIOLLIER

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 by a central metabolic enzyme may be a common mechanism of cellular regulation.

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Methods Mentioned

BETA
Flow cytometry
fluorescence-activated cell sorting
FACS
fluorescence activated cell sorter
fluorescence microscopy
fluorescence imaging
ChIP-Seq
immunoprecipitation
RNA-Seq
two-hybrid

Software Mentioned

CFlow Plus
MicrobeJ
MEM
ImageJ
Galaxy
Progenesis QI
UNIFI
BLAST
Metamorph
bedtools BAM

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