Cell division is antagonized by the activity of peptidoglycan endopeptidases that promote cell elongation

Abstract

A peptidoglycan (PG) cell wall composed of glycans crosslinked by short peptides surrounds most bacteria and protects them against osmotic rupture. In Escherichia coli, cell elongation requires crosslink cleavage by PG endopeptidases to make space for the incorporation of new PG material throughout the cell cylinder. Cell division, on the contrary, requires the localized synthesis and remodeling of new PG at midcell by the divisome. Little is known about the factors that modulate transitions between these two modes of PG biogenesis. In a transposon-insertion sequencing screen to identify mutants synthetically lethal with a defect in the division protein FtsP, we discovered that mutants impaired for cell division are sensitive to elevated activity of the endopeptidases. Increased endopeptidase activity in these cells was shown to interfere with the assembly of mature divisomes, and conversely, inactivation of MepS was found to suppress the lethality of mutations in essential division genes. Overall, our results are consistent with a model in which the cell elongation and division systems are in competition with one another and that control of PG endopeptidase activity represents an important point of regulation influencing the transition from elongation to the division mode of PG biogenesis.

Role of endopeptidases in peptidoglycan synthesis mediated by alternative cross-linking enzymes inEscherichia coli

“…12, and in agreement with a previous study (Cho et al, 2014), the reactions catalyzed by Slt70 and YcbB occur in competition implying that YcbB-mediated cross-linking is not coupled to glycan chain polymerization by RodA. This also implies that YcbB could function in the PG layer in combination with the MepM endopeptidase known to participate in cell elongation (Banzhaf et al, 2020;Singh et al, 2012;Truong et al, 2020;Uehara et al, 2009). In agreement with this model, impaired Slt70 activity had a positive impact on β-lactam resistance mediated by YcbB.…”

Role of endopeptidases in peptidoglycan synthesis mediated by alternative cross‐linking enzymes in Escherichia coli

“…According to the model presented in Fig 12, and in agreement with a previous study (Cho et al, 2014), the reactions catalyzed by Slt70 and YcbB occur in competition implying that YcbB-mediated cross-linking is not coupled to glycan chain polymerization by RodA. This also implies that YcbB could function in the PG layer in combination with the MepM endopeptidase known to participate in cell elongation (Uehara et al, 2009;Singh et al, 2012;Banzhaf et al, 2020;Truong et al, 2020). In agreement with this model, impaired Slt70 activity had a positive impact on b-lactam resistance mediated by YcbB (Fig 12C).…”

Cell wall synthesis and remodeling dynamics determine bacterial division site architecture and cell shape

“…An attractive candidate for this additional synthase is the class A penicillin-binding protein (aPBP) PBP1b. Inactivation of PBP1b has been found to be synthetically lethal with defects in FtsWI activation, and the affected mutants were found to lyse due to septal lesions, suggesting that this aPBP promotes division site stability 35,67 . The location of the wedge at the lagging edge of the division site closest to the OM is also consistent with a role for PBP1b in its construction given that this enzyme and related aPBPs require activation by lipoproteins anchored in the OM to make PG 68,69 .…”

“…Conversely, hyperactivated for the Rod complex were found to be longer than a wild-type control, suggesting that division occurs less frequently when cell elongation is stimulated 75 . Finally, the overproduction of cell wall endopeptidases implicated in cell elongation was found to cause lethal cell division defects in mutants impaired for FtsWI activation 67 . Although these findings are supportive of cell elongation occurring at the expense of division and vice versa, it has remained unclear whether this competition occurs at the level of PG synthesis.…”