Peptidoglycan editing provides immunity to <i>Acinetobacter baumannii</i> during bacterial warfare.

Abstract

Peptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacterium <i>Acinetobacter baumannii</i> strain ATCC 17978 produces, secretes, and incorporates the noncanonical d-amino acid d-lysine into its PG during stationary phase. We show that PG editing increases the competitiveness of <i>A. baumannii</i> during bacterial warfare by providing immunity against peptidoglycan-targeting T6SS effectors from various bacterial competitors. In contrast, we found that d-Lys production is detrimental to pathogenesis due, at least in part, to the activity of the human enzyme d-amino acid oxidase (DAO), which degrades d-Lys producing H₂O₂ toxic to bacteria. Phylogenetic analyses indicate that the last common ancestor of <i>A. baumannii</i> had the ability to produce d-Lys. However, this trait was independently lost multiple times, likely reflecting the evolution of <i>A. baumannii</i> as a human pathogen.