Nitroxoline is a wide spectrum antibacterial and is one of the most important urinary antiseptics.The interaction between nitroxoline and human serum albumin(HSA)has been investigated systematically by fluorescence sp...Nitroxoline is a wide spectrum antibacterial and is one of the most important urinary antiseptics.The interaction between nitroxoline and human serum albumin(HSA)has been investigated systematically by fluorescence spectroscopy,synchronous fluorescence,three-dimensional fluorescence,CD spectroscopy and UV-Vis absorption spectroscopy.The results indicated that the quenching of HSA by nitroxoline was static.The corresponding thermodynamic parameters △H,△S and △G calculated according to van’t Hoff equation revealed that the intermolecular forces acting between nitroxoline and HSA were mainly hydrogen bonding and van der Waals forces.The conformational changes in the interaction were studied by synchronous fluorescence,CD spectroscopy and three-dimensional fluorescence spectra which showed changes in the microenvironment and conformation of HSA.展开更多
Lyme disease(LD),caused by Borrelia burgdorferi,is themost common vector-borne disease in the United States and Europe.Despite the standard 2–4 weeks'antibiotic treatment,approximately 10%–20%of patients will de...Lyme disease(LD),caused by Borrelia burgdorferi,is themost common vector-borne disease in the United States and Europe.Despite the standard 2–4 weeks'antibiotic treatment,approximately 10%–20%of patients will develop posttreatment LD syndrome,a condition that is poorly understood.One of the probable causes is thought to be the presence of B.burgdorferi persister forms that are not effectively killed by the current LD antibiotics.In this study,we evaluated nitroxoline,an antibiotic used to treat urinary tract infections,for its activity against a stationary-phase culture enriched with persister forms of B.burgdorferi.Nitroxoline was found to be more active than doxycycline and equally active as cefuroxime(standard LD antibiotics)against B.burgdorferi.Importantly,the nitroxoline two-drug combinations nitroxoline+cefuroxime and nitroxoline+clarithromycin,as well as the nitroxoline three-drug combination nitroxoline+cefuroxime+clarithromycin,were as effective as the persister drug daptomycin-based positive control three-drug combination cefuroxime+doxycycline+daptomycin,completely eradicating stationary-phase B.burgdorferi in the drug-exposure experiments and preventing regrowth in the subculture study.Future studies should evaluate these promising drug combinations in a persistent LD mouse model.展开更多
基金financially supported by the National Science Fund for Distinguished Young Scholars of China(21225313)the National Natural Science Foundation of China(21303126)+2 种基金Program for Changjiang Scholars and Innovative Research Team in University(IRT1030)Foundation of Hubei Educational Committee(Q20132901)Youth Science Foundation of Huanggang Normal University(2013023903)
文摘Nitroxoline is a wide spectrum antibacterial and is one of the most important urinary antiseptics.The interaction between nitroxoline and human serum albumin(HSA)has been investigated systematically by fluorescence spectroscopy,synchronous fluorescence,three-dimensional fluorescence,CD spectroscopy and UV-Vis absorption spectroscopy.The results indicated that the quenching of HSA by nitroxoline was static.The corresponding thermodynamic parameters △H,△S and △G calculated according to van’t Hoff equation revealed that the intermolecular forces acting between nitroxoline and HSA were mainly hydrogen bonding and van der Waals forces.The conformational changes in the interaction were studied by synchronous fluorescence,CD spectroscopy and three-dimensional fluorescence spectra which showed changes in the microenvironment and conformation of HSA.
基金supported by the Global Lyme Alliance,the Steven and Alexandra Cohen Foundation,the LivLyme Foundation,NatCapLyme,and the Einstein-Sim Family Charitable Fund.
文摘Lyme disease(LD),caused by Borrelia burgdorferi,is themost common vector-borne disease in the United States and Europe.Despite the standard 2–4 weeks'antibiotic treatment,approximately 10%–20%of patients will develop posttreatment LD syndrome,a condition that is poorly understood.One of the probable causes is thought to be the presence of B.burgdorferi persister forms that are not effectively killed by the current LD antibiotics.In this study,we evaluated nitroxoline,an antibiotic used to treat urinary tract infections,for its activity against a stationary-phase culture enriched with persister forms of B.burgdorferi.Nitroxoline was found to be more active than doxycycline and equally active as cefuroxime(standard LD antibiotics)against B.burgdorferi.Importantly,the nitroxoline two-drug combinations nitroxoline+cefuroxime and nitroxoline+clarithromycin,as well as the nitroxoline three-drug combination nitroxoline+cefuroxime+clarithromycin,were as effective as the persister drug daptomycin-based positive control three-drug combination cefuroxime+doxycycline+daptomycin,completely eradicating stationary-phase B.burgdorferi in the drug-exposure experiments and preventing regrowth in the subculture study.Future studies should evaluate these promising drug combinations in a persistent LD mouse model.
