Dual Mechanisms of Action of a Halogenated Allyl Fatty Acid against Methicillin-Resistant <i>Staphylococcus aureus</i>.

ABSTRACT: Antimicrobial resistance in MRSA demands agents with new mechanisms. We evaluated two synthetic unsaturated fatty acids, 2-hexadecynoic acid (2-HDA) and (Z)-2-allyl-3-bromo-2-hexadecenoic acid (DAT-51), across clinical and reference MRSA strains. Both compounds reduced the viability in a dose-dependent manner. Fluorescence microscopy and nucleic acid leakage demonstrated rapid membrane permeabilization; flow cytometry revealed strong depolarization, and SEM showed surface lesions consistent with pore formation. DAT-51 additionally induced Lipid II accumulation and inhibited MurA, whereas lipidomics indicated the selective incorporation of 2-HDA into bacterial phospholipids. Vero-cell assays showed a low cytotoxicity at concentrations exceeding MICs. Together, the data support a dual

SUBMITTER: Villarini-Torres J 

PROVIDER: S-EPMC12658796 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature