title: Nitroxoline: a broad-spectrum biofilm-eradicating agent against pathogenic bacteria.
abstract: Bacterial biofilms are surface-attached communities of slow-growing or non-replicating bacteria tolerant to conventional antibiotic therapies. Although biofilms are known to occur in ca. 80% of all bacterial infections, no therapeutic agent has been developed to eradicate bacteria housed within biofilms. We have discovered that nitroxoline, an antibacterial agent used to treat urinary tract infections, displays broad-spectrum biofilm-eradicating activities against major human pathogens, including drug-resistant Staphylococcus aureus and Acinetobacter baumannii strains. In this study, the effectiveness of nitroxoline to eradicate biofilms was determined using an in vitro [minimum biofilm eradication concentration (MBEC) = 46.9 µM against A. baumannii] and ex vivo porcine skin model (2-3 log reduction in viable biofilm cells). Nitroxoline was also found to eradicate methicillin-resistant S. aureus (MRSA) persister cells in non-biofilm (stationary) cultures, whereas vancomycin and daptomycin were found to be inactive. These findings could lead to effective, nitroxoline-based therapies for biofilm-associated infections.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
authors.forename: Yasmeen
authors.initials: Y
authors.lastname: Abouelhassan
authors.affiliation: Institute of Wound Research, Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
authors.forename: Hussain
authors.initials: H
authors.lastname: Yousaf
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
authors.forename: Minh Thu
authors.initials: MT
authors.lastname: Nguyen
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Rolfe
authors.affiliation: Institute of Wound Research, Department of Obstetrics and Gynecology, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Schultz
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA. Electronic address: rhuigens@cop.ufl.edu.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Huigens
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000502:physiology; D000892:Anti-Infective Agents, Urinary / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D006801:Humans; D009600:Nitroquinolines / Q000494:pharmacology*; D013210:Staphylococcus / Q000187:drug effects* / Q000502:physiology; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects* / Q000502:physiology
chemical_list: D000892:Anti-Infective Agents, Urinary; D009600:Nitroquinolines; C005308:nitroxoline
keywords: Antibiofilm agents; Antibiotic tolerance; Biofilm eradication; Drug discovery; Nitroxoline