Most bacteria contain a mesh-like structure called peptidoglycan (PG) sacculus that helps them to survive osmotic challenges. PG is essential for bacteria and, indeed, some of our best antibiotics, the beta-lactams and glycopeptides, kill bacteria by inhibiting PG synthesis. β-lactam antibiotics target a group of proteins required for the enlargement and remodelling of the PG sacculus, called Penicillin-binding proteins or PBPs. Bacteria keep multiple PBPs and other cell wall enzymes to achieve robust PG growth under a range of environmental conditions. In growing cells of the rod-shaped Escherichia coli new PG material is incorporated into the sacculus within two major stages of the cell cycle, elongation and septation. Specific essential proteins are required for each of these processes, for example PBPs (e.g. PBP2 and PBP3) and cytoskeletal proteins (e.g. MreB and FtsZ), and recent research provided new insights into the functioning of the elongasome and divisome complexes. However, little is known about the transition between both stages when new PG is incorporated at the division site independently of the activity of the essential cell division protein PBP3, and therefore before the septa is built. This is the phase when preseptal PG is synthesized.
In collaboration with groups from CNB-CSIC (Madrid), Indiana University and Utrecht University, we clarify in this paper the role of the cell division protein ZipA during the transition from cell elongation to cell division, and how FtsA and FtsN can compensate for the absence of ZipA. We show that ZipA and FtsA-FtsN have semi-redundant roles in linking the cytosolic Z-ring with PG synthases. In the absence of both linkers, the cells are not viable and are unable to incorporate preseptal PG at the division site. Hence, we show for the first time how PG synthases are connected to the cytokinetic Z-ring, and that the cell establishes this connection even before cell division starts, facilitating a particular phase of PG synthesis. These findings highlight a process required for cell viability, thus generating basic knowledge that could be translated to aid the identification of new antimicrobial drugs.
Manuel Pazos and Waldemar Vollmer