Peptidoglycan editing provides immunity toAcinetobacter baumanniiduring bacterial warfare

AbstractPeptidoglycan (PG) is essential in most bacteria. Thus, it is often targeted by various assaults, including the host immune response, antibiotic treatment and interbacterial attacks via the type VI secretion system (T6SS). Here, we report that the Gram-negative bacteriumAcinetobacter baumanniistrain ATCC 17978 produces, secretes and incorporates the non-canonical D-amino acid D-Lysine into its PG during stationary phase. We show that PG editing increases the competitiveness ofA. baumanniiduring bacterial warfare by providing immunity against peptidoglycan-targeting T6SS effectors from various bacterial competitors. We propose that PG editing has evolved as an effective strategy for bacteria to overcome T6SS attacks. 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 H2O2toxic to bacteria. Phylogenetic analyses indicate that the last common ancestor ofA. baumanniipossessed the ability to produce D-Lys. However, this trait was independently lost multiple times, likely reflecting the evolution ofA. baumanniias a human pathogen.One sentence summaryAcinetobacter baumanniiattains immunity against nonkin competitors during T6SS warfare by incorporating D-Lysine into its peptidoglycan.