Biophysical Society Thematic Meeting | Stockholm 2022

Physical and Quantitative Approaches to Overcome Antibiotic Resistance

Monday Speaker Abstracts

QUANTIFYING THE UPTAKE OF ANTIBIOTICS INTO GRAM-NEGATIVE BACTERIA Mathias Winterhalter Jacobs University, Germany No Abstract

ARE POLYUNSATURATED LIPIDS AN ARCHILLES’ HEEL IN ACINETOBACTER BAUMANNII ANTIMICROBIAL RESISTANCE? Megan L O'Mara 1,3 ; Hugo I MacDermott-Opeskin 1 ; Bart A Eijkelkamp 2 ; Katie A Wilson 1 ; 1 Australian National University, Research School of Chemistry, Canberra, Australia 2 Flinders University, Molecular Sciences and Technology, Adelaide, Australia 3 The University of Queensland, Australian Institute for Bioengineering and Nanotechnology, Brisbane, Australia Gram-negative bacteria such as Acinetobacter baumannii sequester host lipids from the site of infection for incorporation into lipid synthesis pathways, altering the membrane lipidome. Changes in membrane composition from the incorporation of host-derived polyunsaturated fatty acids (PUFAs) help restore sensitivity to antimicrobials in several species of Gram-negative bacteria. 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 show that the changes in A. baumannii membrane biophysical properties on the incorporation of PUFA-containing lipids alters the conformational cycling of RND multidrug efflux pumps and restores sensitivity to some antimicrobials. Finally, we examine the interaction of antimicrobial peptides (AMP) with the simulated A. baumannii membranes to identify the effect of lipid saturation and alterations in membrane properties has on AMP-induced membrane disruption.

9