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

Future Med Chem. 2016;8(3):257-69. doi: 10.4155/fmc.15.189. Epub 2016 Feb 24.


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.

Keywords: MRSA; NH125; antibiotics; giant unilamellar vesicle; two-component system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Cell Membrane Permeability / drug effects
  • Dose-Response Relationship, Drug
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Lipid Bilayers / metabolism*
  • Methicillin-Resistant Staphylococcus aureus / cytology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Structure-Activity Relationship


  • Anti-Bacterial Agents
  • Imidazoles
  • Lipid Bilayers
  • NH 125