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

Wooseong Kim, Nico Fricke, Annie L. Conery, Beth Burgwyn Fuchs, Rajmohan Rajamuthiah, Elamparithi Jayamani, Petia M. Vlahovska, Frederick M. Ausubel, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish
Pages (from-to)257-269
Number of pages13
JournalFuture Medicinal Chemistry
Volume8
Issue number3
DOIs
StatePublished - Mar 2016

Keywords

  • MRSA
  • NH125
  • antibiotics
  • giant unilamellar vesicle
  • two-component system

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