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 language | English (US) |
|---|---|
| Pages (from-to) | 257-269 |
| Number of pages | 13 |
| Journal | Future Medicinal Chemistry |
| Volume | 8 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 2016 |
Keywords
- MRSA
- NH125
- antibiotics
- giant unilamellar vesicle
- two-component system
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology
- Drug Discovery
Divisions
- Infectious Disease
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