The Bacterial Cell Wall: Localizing Enzymes Required for Peptidoglycan Synthesis in the Presence of ?-lactam Antibiotics

Abstract

Bacteria are surrounded by a peptidoglycan (PG) cell wall that protects them from lysis due to turgor pressure. ?-lactam antibiotics work by inactivating penicillin-binding proteins (PBPs) that synthesize the cell wall. E.coli has four PBPs. One of these is essential for elongation (PBP2) and another for division (PBP3), but the roles of PBP1a and PBP1b are unclear. Previously, the Weiss lab observed that a GFP-PBP1b fusion protein accumulated at division sites when PBP3 was inactivated with the ?-lactam cephalexin. This finding suggests PBP1b might be a repair enzyme that localizes to sites where the cell wall is damaged. Here we artificially produced three foreign PBPs from Pseudomonas and Vibrio in E. coli. Two of the foreign PBPs localized to division sites when cells were treated with cephalexin. These foreign PBPs are only 21-38% identical in amino acid sequence to E. coli PBP1b. That makes the foreign PBPs too diverged to interact productively with any E. coli proteins. In contrast, the structure of PG is highly conserved among these bacteria. We conclude that septal localization of the PBPs is likely driven by recognition of some form of damaged or aberrant PG, with the intent to repair it.