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

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

Author information

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.

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

PMID:
26910612
PMCID:
PMC4976882
[Available on 2017-03-01]
DOI:
10.4155/fmc.15.189
[Indexed for MEDLINE]
Free PMC Article
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