Cell cycle control by the master regulator CtrA in Sinorhizobium meliloti

In order to propagate, all living cells must ensure that their genetic material is faithfully copied and properly partitioned into the daughter cells before division. These coordinated processes of DNA replication and cell division are termed the “cell cycle” and are controlled by a complex network of regulatory proteins in all organisms. In the class Alphaproteobacteria, the regulation of the cell cycle is closely linked to cellular differentiation processes that are vital for survival in the environment. In these bacteria, the cell cycle regulator CtrA is thought to serve as the primary link between the coordination of the cell cycle and cellular differentiation. The alphaproteobacterium, Sinorhizobium meliloti, an important model symbiont of alfalfa plants, undergoes a striking cellular differentiation that is vital to the formation of an efficient symbiosis dedicated to the conversion of atmospheric nitrogen to biologically available organic nitrogen. However, the link between cellular differentiation and cell cycle control in S. meliloti has not been made. In this study, we showed that S. meliloti cells without CtrA are similar to the symbiotic form. By the identification of the genes whose expression is directly and indirectly controlled by CtrA, we found that CtrA regulates vital cell cycle processes, including DNA replication and cell division, but through different genetic pathways than in other alphaproteobacteria. We importantly show that the levels of CtrA protein are governed by an essential cell cycle regulated proteolysis, which may also be an important mode of CtrA down-regulation during symbiosis to drive cellular differentiation.