Cell size regulation in bacteria: a tale of old regulators with new mechanisms

Proper function in a bacterial cell relies on intrinsic cell size regulation. The molecular mechanisms underlying how bacteria maintain their cell size remain unclear. The conserved regulator DnaA, the initiator of chromosome replication, is associated to size regulation by controlling the number of origins of replication (oriC) per cell. In this study, we identify and characterize a new mechanism in which DnaA modulates cell size independently of oriC-copy number. By altering the levels of DnaA without impacting chromosome replication, we demonstrate that DnaA's activity as a transcription factor can slow down cell elongation rate resulting in cells that are ~20% smaller. We identify the peptidoglycan biosynthetic enzyme MurD as a key player of cell size regulation in Caulobacter crescentus and in the evolutionarily distant bacterium Escherichia coli. Collectively, our findings provide mechanistic insights to the complex regulation of cell size in bacteria.