A global view of morphogenetic peptidoglycan synthases across the domain Bacteria.

Abstract

Bacteria define their heritable cell shape using membrane integral glycosyltransferases (GTases) of the shape, elongation, division, and sporulation protein family and monofunctional D, D-transpeptidases of the class B penicillin-binding protein family (bPBP). Current models support bPBPs pairing with cognate GTases to drive cell elongation, cell division, or spore formation. Recent studies in Salmonella enterica and Clostridioides difficile however support different models with more than one bPBP interacting with a particular GTase. Here, we mined databases to assess how this plasticity in interacting proteins is represented across the domain Bacteria. Like Salmonella, many bacteria of Enterobacterales encode alternative bPBPs while having a single set of morphogenetic GTases. When extended to the domain Bacteria, the analysis uncovered bPBPs lacking the pedestal domain required to interact with the GTase and GTases with β-sheet-rich regions facing outward from the membrane. We also identified large size chimeric bPBPs fused to a GTase (FtsW/RodA/SpoVE) domain as putative 'bifunctional' class B peptidoglycan synthases. Alteration of the bPBP:GTase 1:1 ratio appears as common feature, in some cases with unbalanced proliferation of both partners or with absence of one canonical bPBP (MrdA or FtsI). Bacteria were also found with some morphogenetic functions counter-selected involving pseudogenization in highly conserved loci like ftsI, mrdA, mreC, or spoVE. Most of these bacteria encode non-canonical bPBPs bearing a PBP-A dimerisation domain instead of the canonical pedestal domain. Altogether, our findings challenge classical morphogenetic models and predict in many bacteria significant flexibility in how bPBPs and GTases combine to define cell shape.