FtsW is a peptidoglycan polymerase that is functional only in complex with its cognate penicillin-binding protein

The peptidoglycan cell wall is essential for the survival and morphogenesis of bacteria.(1) For decades it was thought that only class A penicillin-binding proteins (aPBPs) and related enzymes effected peptidoglycan synthesis. Recently, it was shown that RodA, a member of the unrelated SEDS protein family, also acts as a peptidoglycan polymerase.(2–4) Not all bacteria require RodA for growth; however, its homologue, FtsW, is a core member of the divisome complex that appears to be universally essential for septal cell wall assembly.(5,6) FtsW was previously proposed to translocate the peptidoglycan precursor Lipid II across the cytoplasmic membrane.(7,8) We report here that purified FtsW polymerizes Lipid II into peptidoglycan, but show that its polymerase activity requires complex formation with its partner class B PBP (bPBP). We further demonstrate that the polymerase activity of FtsW is required for its function in vivo. Thus, our findings establish FtsW as a peptidoglycan polymerase that works with its cognate bPBP to produce septal peptidoglycan during cell division.