要旨
Bacteria display a high morphological diversity, ranging from spheres to rods and spirals that tremendously vary in size. Similarly, the bacterial envelope has evolved and adapted to different environments in response to evolutionary pressure, resulting in variations in the composition of the cell wall, type and amount of lipids and accessory proteins, thickness, and the presence or absence of an outer membrane. Despite these variations, cell division is a crucial event to generate progeny, which all bacteria have in common and perform in almost the same manner: determination of the cell division site, assembly of a multi-enzyme complex (divisome), and constriction of one or both cell membranes by the formation of a septum, which is realized by remodeling of the peptidoglycan (PG), resulting in the compartmentalization of the cytoplasm and release of the daughter cells. During cell division, PG synthesis provides the force and directionality for constriction of the cell envelope. Thus, many studies have focused over the past decade on proteins involved in PG remodeling during cytokinesis. However, these studies were mainly done in the model organism Escherichia coli, leading to a lack of knowledge in another model organism, such as the Alphaproteobacterium Caulobacter crescentus. In this study, I investigated the functional dynamics of bifunctional penicillin-binding proteins (bPBPs) of C. crescentus and focused on their role during cell division. Two out of five bPBPs, namely PbpX and PbpY, were identified to be specifically involved in septal PG remodeling. Furthermore, it was shown that their midcell localization is dependent on the late essential cell division protein FtsN, consistent with the finding that PbpX and PbpY are late recruits to the division site. Moreover, they likely interact with FtsL and the putative PG hydrolase DipM, forming a multi-enzyme complex that mediates PG remodeling. In addition, it was demonstrated that, in principle, all bPBPs, except for PbpZ, are functionally redundant and can take over the role of the others, implying that all of them have retained the ability to interact with the divisome. However, each bPBP may preferentially act in specific biosynthetic complexes but additionally be able to provide robust PG synthesis under conditions of intra- or extracellular stress. In addition to constriction of the cell envelope, bacteria also need to ensure faithful distribution of the replicated sister chromosomes to each daughter cell. To this end, cells require a tight spatiotemporal regulation of DNA replication and segregation of each chromosome copy, to create a DNA-free division plane. Accordingly, the timing of cell division and PG remodeling must be flexible and intimately linked to chromosome dynamics. However, the temporal control mechanisms of cell division are still largely unknown, even in the well-studied model organisms. Here, I report a novel cell division protein CedC, which is a late recruit to the division site and may regulate the timing of cell division in response to the status of DNA at the division plane at the final stage of cell division. It is hypothesized that CedC could constitute a checkpoint that recognizes chromosome dimers at the division site via direct or indirect interaction with the tyrosine-recombinase XerC and FtsA, which slows down PG synthesis. In this way, cells would gain time to resolve chromosome dimers, resulting in faithful distribution of the sister chromosomes and successful division.
