FtsA acts through FtsW to promote cell wall synthesis during cell division in Escherichia coli

• Published in: Proceedings of the National Academy of Sciences - PNAS 2021-08, Vol.118 (35), p.1-12
• Main Authors: Park, Kyung-Tae, Pichoff, Sebastien, Du, Shishen, Lutkenhaus, Joe
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biological Sciences; Cell Division; Cell Wall - metabolism; Cell walls; Conformation; Cytokinesis; Cytoplasm; E coli; Escherichia coli; Escherichia coli - genetics; Escherichia coli - growth & development; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Escherichia coli Proteins - metabolism; Filaments; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mutants; Peptidoglycans; Periplasm; Recruitment; Switches; Synergism; Synthesis
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2107210118

In Escherichia coli, FtsQLB is required to recruit the essential septal peptidoglycan (sPG) synthase FtsWI to FtsA, which tethers FtsZ filaments to the membrane. The arrival of FtsN switches FtsQLB in the periplasm and FtsA in the cytoplasm from a recruitment role to active forms that synergize to activate FtsWI. Genetic evidence indicates that the active form of FtsQLB has an altered conformation with an exposed domain of FtsL that acts on FtsI to activate FtsW. However, how FtsA contributes to the activation of FtsW is not clear, as it could promote the conformational change in FtsQLB or act directly on FtsW. Here, we show that the overexpression of an activated FtsA (FtsA*) bypasses FtsQ, indicating it can compensate for FtsQ’s recruitment function. Consistent with this, FtsA* also rescued FtsL and FtsB mutants deficient in FtsW recruitment. FtsA* also rescued an FtsL mutant unable to deliver the periplasmic signal from FtsN, consistent with FtsA* acting on FtsW. In support of this, an FtsW mutant was isolated that was rescued by an activated FtsQLB but not by FtsA*, indicating it was specifically defective in activation by FtsA. Our results suggest that in response to FtsN, the active form of FtsA acts on FtsW in the cytoplasm and synergizes with the active form of FtsQLB acting on FtsI in the periplasm to activate FtsWI to carry out sPG synthesis.