TY - JOUR
T1 - NH125 kills methicillin-resistant Staphylococcus aureus persisters by lipid bilayer disruption
AU - Kim, Wooseong
AU - Fricke, Nico
AU - Conery, Annie L.
AU - Fuchs, Beth Burgwyn
AU - Rajamuthiah, Rajmohan
AU - Jayamani, Elamparithi
AU - Vlahovska, Petia M.
AU - Ausubel, Frederick M.
AU - Mylonakis, Eleftherios
N1 - Publisher Copyright:
© 2016 Future Science Ltd.
PY - 2016/3
Y1 - 2016/3
N2 - 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.
AB - 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.
KW - MRSA
KW - NH125
KW - antibiotics
KW - giant unilamellar vesicle
KW - two-component system
UR - http://www.scopus.com/inward/record.url?scp=84960111425&partnerID=8YFLogxK
U2 - 10.4155/fmc.15.189
DO - 10.4155/fmc.15.189
M3 - Article
C2 - 26910612
AN - SCOPUS:84960111425
SN - 1756-8919
VL - 8
SP - 257
EP - 269
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 3
ER -