NH125 kills methicillin-resistant Staphylococcus aureus persisters by lipid bilayer disruption

Future Medicinal Chemistry
Wooseong KimEleftherios Mylonakis

Abstract

NH125, a known WalK inhibitor kills MRSA persisters. However, its precise mode of action is still unknown. 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. NH125 kills MRSA persisters by interacting with and disrupting membranes in a detergent-like manner.

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Citations

Apr 13, 2017·Expert Opinion on Drug Discovery·Wooseong KimEleftherios Mylonakis
Mar 24, 2017·FEMS Microbiology Reviews·Bram Van den BerghJan Michiels
May 23, 2017·Nature Reviews. Microbiology·Robert A FisherSophie Helaine
Nov 4, 2017·The Journal of Membrane Biology·Silvia T CardonaAndrew M Hogan
Mar 24, 2018·Future Medicinal Chemistry·Wooseong KimEleftherios Mylonakis
May 18, 2020·Applied Microbiology and Biotechnology·Lasse van GeelenRainer Kalscheuer
Jul 31, 2019·Proceedings of the National Academy of Sciences of the United States of America·Wooseong KimEleftherios Mylonakis
May 29, 2020·The Journal of Microbiology·Soo Min KimWooseong Kim
Feb 28, 2019·Chembiochem : a European Journal of Chemical Biology·Robert W HuigensHongfen Yang
May 20, 2017·Annual Review of Phytopathology·T Shidore, L R Triplett

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