Checks and Balances in Bacterial Cell Division

Abstract

Assembly of the division machinery in Gram-negative and Gram-positive bacteria occurs in two time-dependent steps. First, the FtsZ proto-ring localizes at midcell including some FtsN molecules. Subsequently, the proteins that catalyze and regulate septal peptidoglycan (PG) synthesis are recruited including among others, the FtsBLQ-PB1B-FtsW-PBP3 complex. Further accumulation of FtsN finally allows initiation of cell division. It was known that FtsA and FtsQLB somehow prevented this initiation. Recently, A. Boes, S. Olatunji, E. Breukink, and M. Terrak (mBio 10:e01912-18, 2019, https://doi.org/10.1128/mBio.01912-18) reported that this is caused by inhibition of the activity of the PG synthases by FtsBLQ, which has to be outcompeted by accumulation of the PBP1b activating FtsN. This supports a central structural as well as regulatory role for the FtsBLQ protein complex that is conserved only in prokaryotes, making it an attractive target for antibiotic development.

Keywords: Escherichia coli; cell division; divisome; peptidoglycan.

FIG 1

Schematic representation of the possible interactions and activation in the divisome. Panel A shows the divisome when FtsN is initially recruited by FtsA (31). For the model, only the relevant divisome proteins are shown. This switches FtsA to the on state, and further accumulation of FtsN allows successful competition with FtsBLQ for the peptidoglycan synthetic complex shown in panel B. FtsN activates PBP1B, which becomes hyperactive due to the absence of CpoB. The concomitant abolishment of PBP3 inhibition allows FtsW activity and the initiation of septal PG synthesis. Since none of the PG hydrolases are included in the model, at this time, we assume that the regulation of septation will be more complex than shown here.