Altered regulation of septal peptidoglycan synthesis modulates β-lactam susceptibility in <i>Pseudomonas aeruginosa</i>

The useful part

Marmont Bacterial cell division requires precise regulation of septal peptidoglycan (PG) synthesis by the essential SEDS-bPBP synthase FtsWI. Here, using the conditional essentiality of ftsN in Pseudomonas aeruginosa, we identify substitutions in the non-enzymatic pedestal domain of FtsI that bypass the requirement for FtsN. aeruginosa FtsQLBWI structure reveals that they cluster on distinct surfaces of the pedestal domain.

How it works

• These findings show that the FtsI pedestal domain plays a central role in the regulation of FtsWI and reveal a previously unrecognized relationship between divisome regulation and β-lactam susceptibility.
• More broadly, our work identifies the pedestal domain as a regulatory hub that integrates multiple inputs controlling septal PG synthesis and highlights its potential relevan...
• aeruginosa isolates with increased aztreonam resistance, we next asked whether these regulatory substitutions alter β-lactam susceptibility.

What to take from it

Because some of these substitutions have been identified in clinical P.

Details worth keeping

Activation of FtsWI is thought to occur through an allosteric cascade initiated by the late-arriving divisome protein FtsN and transmitted via the FtsQ-FtsL-FtsB (FtsQLB) complex, but the molecular details of this process remain incompletely defined and differ across species. These mutations restore cell division in Δ ftsN cells, suppress dominant-negative phenotypes of activation-defective ftsL alleles, and reduce cell length in an otherwise wild-type background, demonstrating that they alter FtsWI regulation to overcome the requirement for stimulation by both FtsN and FtsQLB. Variants at the FtsI-FtsL interface modestly reduce susceptibility to multiple β-lactam antibiotics, whereas a variant on the opposite face of the pedestal domain produces striking FtsN-dependent hypersusceptibility to the same molecules.