Lipidome modifications in A. baumannii alter membrane properties and antimicrobial peptide interactions

The gram-negative pathogen Acinetobacter baumannii is a primary contributor to nosocomial multidrug resistant (MDR) infections. To combat the rise of MDR infections, novel features of A. baumannii need to be considered for the development of new treatment options. One such feature is the preferential scavenging of exogenous lipids, including host-derived polyunsaturated fatty acids (PUFAs), for incorporation into membrane phospholipid synthesis pathways. These alterations in membrane composition impact both the lipid chemistry and the membrane biophysical properties. Using coarse-grained simulations based on lipidomic data of A. baumannii inner membrane collected under three different growth conditions, we show PUFA-incorporation alters membrane biophysical properties, increasing the phase separation between ordered and disordered lipid domains resulting in thinner, less ordered membranes. We examine how PUFA-incorporation impacts RND efflux pump stability and alters the interaction of four prototypical AMPs with the membrane. We find that both lipid headgroup and tail unsaturation played distinct roles in driving membrane/protein interactions. Cumulatively, this work highlights the importance of capturing lipidome modifications when examining bacterial multidrug resistance.