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.
Wooseong Kim  1 ,  Nico Fricke  2 ,  Annie L Conery  3  4 ,  Beth Burgwyn Fuchs  1 ,  Rajmohan Rajamuthiah  1  3 ,  Elamparithi Jayamani  1  3 ,  Petia M Vlahovska  2 ,  Frederick M Ausubel  3  4 ,  Eleftherios Mylonakis  1
Affiliations
  • 1. Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
  • 2. School of Engineering, Brown University, Providence, RI, USA.
  • 3. Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
  • 4. Department of Genetics, Harvard Medical School, Boston, MA, USA.
PMID: 26910612 DOI: 10.4155/fmc.15.189
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.

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