We are what we eat: identifying a regulatory crosstalk between central carbon metabolism and cell division in bacteria

Mann R1, Bottomley AL1, Monahan LG1, Sonenshein AL2 and Harry EJ1

  1. The ithree Institute, University of Technology Sydney, Ultimo, Australia.
  2. Tufts University, Boston, Massachusetts, United States of America.

Cell division, an essential process in bacteria, is driven by a cytoskeletal ring structure - the Z ring, whose formation at midcell site must be tightly regulated to ensure faithful cell division. Several mechanisms have previously been described that influence the positioning and timing of Z ring assembly, but one important yet poorly understood aspect of cell division regulation is the need to coordinate division with cell growth and nutrient availability. We have demonstrated for the first time the role of central carbon metabolism (CCM) in Z ring formation in the bacterium Bacillus subtilis. A mutant of the glycolytic enzyme pyruvate kinase (pyk), which produces pyruvate in the final step of glycolysis, was shown to form acentral Z rings. This Z ring placement defect, however, was rescued when pyruvate was added to the growth medium, signifying pyruvate to be a specific key metabolite in coordinating cell growth with division by regulating midcell Z ring formation. Along with validating a previous observation that the pyk mutant displays a DNA replication underinitiation phenotype, we have also found that the addition of pyruvate rescues this underinitiation defect of Δpyk cells. This observation correlates with the Z ring placement rescue observed after pyruvate addition and raises the possibility that pyruvate is involved in cell division regulation via its effect on the DNA replication process. Overall, we hypothesize that the metabolic regulation of the division process is indeed an outcome of the effect that metabolic perturbation has on the DNA replication process. Understanding this interconnection between various cell cycle events not only helps us answer some of the age-old basic biology questions, but also uncovers a new area of interest for possible exploitation for the development of antimicrobial agents.