Hit the right spots: cell cycle control by phosphorylated guanosines in alphaproteobacteria

Key Points Alphaproteobacteria are Gram-negative bacteria that have heterogeneous lifestyles, including aquatic and soil-dwelling lineages, endosymbionts, pathogens of plants, arthropods or mammals, as well as the ancestors of eukaryotic mitochondria. The phosphorylated guanosines cyclic di-GMP (c-di-GMP), and guanosine tetraphosphate and guanosine pentaphosphate (collectively referred to as (p)ppGpp) act as antagonistic second messengers that control the progression of the cell cycle in Alphaproteobacteria. The intracellular concentration of c-di-GMP surges at the G1–S transition of the cell cycle in Caulobacter crescentus to stimulate the initiation of DNA replication, and c-di-GMP coordinates remodelling of the differentiating pole. c-di-GMP regulates the proteolytic degradation of key regulators of the cell cycle. The alarmone (p)ppGpp promotes the swarmer phase of C. crescentus cells by delaying the initiation of DNA replication and polar differentiation. The alarmone is crucial for several Rhizobiales to sustain symbiotic or pathogenic relationships with their respective eukaryotic host cells.