Characterizing the role of phosphatidylglycerol-phosphate phosphatases in Acinetobacter baumannii cell envelope biogenesis and antibiotic resistance

Abstract

The dissemination of multi-drug resistant Acinetobacter baumannii threatens global healthcare systems and necessitates the development of novel therapeutic options. The Gram-negative bacterial cell envelope provides a first defensive barrier against antimicrobial assault. Essential components of this multi-layered complex are the phospholipid-rich membranes. Phosphatidylglycerol phosphate (PGP) phosphatases are responsible for a key step in the biosynthesis of a major phospholipid species, phosphatidylglycerol (PG), but these enzymes have also been implicated in the biogenesis of other cell envelope components. Our bioinformatics analyses identified two putative PGP candidates in the A. baumannii genome, PgpA and PgpB. Phospholipid analyses of isogenic pgpA mutants in two distinct A. baumannii strains revealed a shift in the desaturation levels of phosphatidylethanolamine (PE) phospholipid species, possibly due to the activation of the phospholipid desaturase DesA. We also investigated the impact of the inner membrane phosphatases on other cell envelope components, which revealed a role of PgpB in the maintenance of the A. baumannii peptidoglycan layer, and consequently carbapenem resistance. Collectively, this work provides novel insights into the roles of PGP phosphatases on the global lipidomic landscape of A. baumannii and their interconnectivity with the biogenesis of other cell envelope components. The non-essentiality of these candidates exemplifies metabolic versatility of A. baumannii, which is believed to be key to its success as global pathogen.