Functional redundancy of division specific penicillin‐binding proteins in Bacillus subtilis

Summary Bacterial cell division involves the dynamic assembly of a diverse set of proteins that coordinate the invagination of the cell membrane and synthesis of cell wall material to create the new cell poles of the separated daughter cells. Penicillin‐binding protein PBP 2B is a key cell division protein in Bacillus subtilis proposed to have a specific catalytic role in septal wall synthesis. Unexpectedly, we find that a catalytically inactive mutant of PBP 2B supports cell division, but in this background the normally dispensable PBP 3 becomes essential. Phenotypic analysis of pbpC mutants (encoding PBP 3) shows that PBP 2B has a crucial structural role in assembly of the division complex, independent of catalysis, and that its biochemical activity in septum formation can be provided by PBP 3. Bioinformatic analysis revealed a close sequence relationship between PBP 3 and Staphylococcus aureus PBP 2A, which is responsible for methicillin resistance. These findings suggest that mechanisms for rescuing cell division when the biochemical activity of PBP 2B is perturbed evolved prior to the clinical use of β‐lactams. The bacterial division complex is a dynamic assembly of multiple proteins. Here, we show that the essential Penicillin Binding Protein 2B (PBP 2B) has a redundant biochemical activity, but an essential structural role in complex formation. Whereas, PBP 3 can act to provide the biochemical activity required for division but is not able to functionally replace PBP 2B. The results provide a functional role for PBP 3 in Bacillus subtilis and may suggest how penicillin resistance has evolved.