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  • Title: NH125 kills methicillin-resistant Staphylococcus aureus persisters by lipid bilayer disruption.
    Author: Kim W, Fricke N, Conery AL, Fuchs BB, Rajamuthiah R, Jayamani E, Vlahovska PM, Ausubel FM, Mylonakis E.
    Journal: Future Med Chem; 2016; 8(3):257-69. PubMed ID: 26910612.
    Abstract:
    BACKGROUND: NH125, a known WalK inhibitor kills MRSA persisters. However, its precise mode of action is still unknown. METHODS & RESULTS: The mode of action of NH125 was investigated by comparing its spectrum of antimicrobial activity and its effects on membrane permeability and giant unilamellar vesicles (GUVs) with walrycin B, a WalR inhibitor and benzyldimethylhexadecylammonium chloride (16-BAC), a cationic surfactant. NH125 killed persister cells of a variety of Staphylococcus aureus strains. Similar to 16-BAC, NH125 killed MRSA persisters by inducing rapid membrane permeabilization and caused the rupture of GUVs, whereas walrycin B did not kill MRSA persisters or induce membrane permeabilization and did not affect GUVs. CONCLUSION: NH125 kills MRSA persisters by interacting with and disrupting membranes in a detergent-like manner.
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