Uncovering Unappreciated Activities and Niche Functions of Bacterial Cell Wall Enzymes

A peptidoglycan (PG) cell wall is an essential component of nearly all bacteria, providing protection against turgor pressure. Metabolism of this PG meshwork must be spatially and temporally regulated in order to support cell growth and division. Despite being an active area of research for decades, we have only recently identified the primary PG synthesis complexes that function during cell elongation (RodA-PBP2) and cell division (FtsW-FtsI), and we are still uncovering the importance of the other seemingly redundant cell wall enzymes. In this minireview, we highlight the discovery of the monofunctional glycosyltransferases RodA and FtsW and describe how these findings have prompted a re-evaluation of the auxiliary role of the bifunctional class A penicillin-binding proteins (aPBPs) as well as the L,D-transpeptidases (LDTs). Specifically, recent work indicates that the aPBPs and LDTs function independently of the primary morphogenetic complexes to support growth, provide protection from stresses, mediate morphogenesis, and/or allow adaptation to different growth conditions. These paradigm-shifting studies have reframed our understanding of bacterial cell wall metabolism, which will only become more refined as emerging technology allows us to tackle the remaining questions surrounding PG biosynthesis.