title: NH125 kills methicillin-resistant Staphylococcus aureus persisters by lipid bilayer disruption.
abstract: BACKGROUND
  NH125, a known WalK inhibitor kills MRSA persisters. However, its precise mode of action is still unknown.
  
  
  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.
  
  
  CONCLUSIONS
  NH125 kills MRSA persisters by interacting with and disrupting membranes in a detergent-like manner.
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Kim
authors.affiliation: School of Engineering, Brown University, Providence, RI, USA.
authors.forename: Nico
authors.initials: N
authors.lastname: Fricke
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.|Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Annie L
authors.initials: AL
authors.lastname: Conery
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Beth Burgwyn
authors.initials: BB
authors.lastname: Fuchs
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.|Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Rajmohan
authors.initials: R
authors.lastname: Rajamuthiah
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.|Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Elamparithi
authors.initials: E
authors.lastname: Jayamani
authors.affiliation: School of Engineering, Brown University, Providence, RI, USA.
authors.forename: Petia M
authors.initials: PM
authors.lastname: Vlahovska
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA.|Department of Genetics, Harvard Medical School, Boston, MA, USA.
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Ausubel
authors.affiliation: Division of Infectious Diseases, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000378:metabolism*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000166:cytology* / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D007093:Imidazoles; D008051:Lipid Bilayers; C414024:NH 125
keywords: MRSA; NH125; antibiotics; giant unilamellar vesicle; two-component system