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*

*Corresponding author for this work

Research output: Contribution to journalArticle

22 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 (US)
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

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery

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    Kim, W., Fricke, N., Conery, A. L., Fuchs, B. B., Rajamuthiah, R., Jayamani, E., Vlahovska, P. M., Ausubel, F. M., & Mylonakis, E. (2016). NH125 kills methicillin-resistant Staphylococcus aureus persisters by lipid bilayer disruption. Future Medicinal Chemistry, 8(3), 257-269. https://doi.org/10.4155/fmc.15.189