The pH-dependence of lipid-mediated antimicrobial peptide resistance in a model staphylococcal plasma membrane: A two-for-one mechanism of epithelial defence circumvention

摘要: Abstract The mechanisms of membrane defence by lysylphosphatidylglycerol (LPG), were investigated using synthetic biomimetic mono- and bilayer models methicillin resistant S. aureus ST239 TW, based on its lipid composition in both pH 7.4 (28% LPG) pH 5.5 (51% cultures. These incorporated a stable analogue LPG (3adLPG) to facilitate long-duration biophysical studies, which previously limited the lability native LPG. Both increased 3adLPG content full headgroup ionization at pH 5.5, order dampened overall charge, via formation neutral ion pairs with anionic lipids. Ion pair air/liquid interface monolayers elicited significant condensing effect, correlated inhibition subphase-injected magainin 2 F5W partitioning. In fluid phase vesicles, increasing proportion from 28 51 mol% completely inhibited adoption membrane-active α‑helical conformation peptide, without need for ionization. Neutron reflectivity measurements performed PG/3adLPG floating bilayers, showed ordering effect mild acidity containing 30 mol% 3adLPG, whilst peptide binding/partitioning was only fully 55 mol% pH 5.5. findings are discussed respect roles resistance human epithelial defences continued evolution this opportunistic pathogen's virulence.