Membrane-targeted mechanism for amphiphilic vitamin C compounds as methicillin-resistant Staphylococcus aureus biofilm eradicating agents

Abstract

Staphylococcus aureus infections and its biofilm removal is an important concern in health care management. Methicillin-resistant S. aureus is responsible for severe morbidity and mortality worldwide. A new strategy in the search for novel antimicrobials is approached by developing new molecules capable of targeting and disrupting bacterial membranes. The alkyl esters of L-ascorbic acid (ASCn) are antioxidant amphiphiles, which show antimicrobial capacity against methicillin-sensitive and resistant S. aureus strains. ASC12 and ASC14 formulations are also able to kill the persister cells of the deepest layers of the biofilm. ASC16 appears as a poor antimicrobial and antibiofilm agent. We tested the hypothesis that the antimicrobial and antibiofilm capacity found for the ASCn emerges from a combined effect of its amphiphilic and their redox capacity. This mechanism appears related to: I) a larger diffusion capacity of the ASC12 micelles than ASC14 and ASC16 microstructures; II) the neutralization of the ASCn acid hydroxyl when the amphiphile reaches the surface of an anionic surface, followed by a rapid insertion; III) the disruption of cell membrane by alteration of membrane tension and structure and IV) ASCn accumulation in the cell membrane or biofilm extracellular matrix surfaces, reducing functional chemical groups and affecting its biological function.