DipM controls multiple autolysins and mediates a regulatory feedback loop promoting cell constriction in Caulobacter crescentus

Proteins containing a catalytically inactive LytM-type endopeptidase domain are important regulators of cell wall-degrading enzymes in bacteria. Here, we study their representative DipM, a factor mediating proper cell division in Caulobacter crescentus. We show that the LytM domain of DipM interacts with mul-tiple autolysins, including the lytic transglycosylases SdpA and SdpB, the amidase AmiC and the putative carboxypeptidase CrbA, and stimulates the activities of SdpA and AmiC. Its crystal structure displays a conserved groove, which is predicted to represent the dock¬ing site for autolysins by model¬ing studies. Mutations in this groove indeed abolish the function of DipM in vivo and its interaction with AmiC and SdpA in vitro. Notably, DipM and its regulatory targets SdpA and SdpB stimulate each other’s recruitment to the division site, establishing a self-reinforcing cycle that gradually increases autolytic activity as cyto¬kinesis progresses. DipM thus acts at the intersection of different peptidoglycan-remodeling pathways and coordinates their activities to ensure proper cell constriction and daughter cell separation.