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 - Funding Information:
This study was supported by NIH grant P01 AI083214 to EE Mylonakis and FM Ausubel. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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 - antibiotics
KW - giant unilamellar vesicle
KW - MRSA
KW - NH125
KW - two-component system
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U2 - 10.4155/fmc.15.189
DO - 10.4155/fmc.15.189
M3 - Article
C2 - 26910612
AN - SCOPUS:84960111425
VL - 8
SP - 257
EP - 269
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
SN - 1756-8919
IS - 3
ER -