title: Efficient Reduction of Antibacterial Activity and Cytotoxicity of Fluoroquinolones by Fungal-Mediated N-Oxidation.
abstract: Extensive usage of fluoroquinolone antibiotics in livestock results in their occurrence in manure and subsequently in the environment. Fluoroquinolone residues may promote bacterial resistance and are toxic to plants and aquatic organisms. Moreover, fluoroquinolones may enter the food chain through plant uptake, if manure is applied as fertilizer. Thus, the presence of fluoroquinolones in the environment may pose a threat to human and ecological health. In this study, the biotransformation of enrofloxacin, marbofloxacin, and difloxacin by the fungus X. longipes (Xylaria) was investigated. The main metabolites were unequivocally identified as the respective N-oxides by mass spectrometry and nuclear magnetic resonance spectroscopy. Fungal-mediated N-oxidation of fluoroquinolones led to a 77-90% reduction of the initial antibacterial activity. In contrast to their respective parent compounds, N-oxides showed low cytotoxic potential and had a reduced impact on cell proliferation. Thus, biotransformation by X. longipes may represent an effective method for inactivating fluoroquinolones.
authors.affiliation: Justus Liebig University Giessen , Institute of Food Chemistry and Food Biotechnology, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.
authors.forename: Marina
authors.initials: M
authors.lastname: Rusch
authors.affiliation: Justus Liebig University Giessen , Institute of Food Chemistry and Food Biotechnology, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Spielmeyer
authors.affiliation: University of Veterinary Medicine Hannover Foundation , Institute of Pharmacology, Toxicology and Pharmacy, Buenteweg 17, 30559 Hannover, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Meißner
authors.affiliation: University of Veterinary Medicine Hannover Foundation , Institute of Pharmacology, Toxicology and Pharmacy, Buenteweg 17, 30559 Hannover, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kietzmann
authors.affiliation: Justus Liebig University Giessen , Institute of Food Chemistry and Food Biotechnology, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.|Fraunhofer IME , Project Group Bioresources, 35392 Giessen, Germany.
authors.forename: Holger
authors.identifier: http://orcid.org/0000-0002-8383-8196
authors.initials: H
authors.lastname: Zorn
authors.affiliation: Justus Liebig University Giessen , Institute of Food Chemistry and Food Biotechnology, Heinrich-Buff-Ring 17, 35392 Giessen, Germany.
authors.forename: Gerd
authors.identifier: http://orcid.org/0000-0002-5137-5510
authors.initials: G
authors.lastname: Hamscher
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024841:Fluoroquinolones / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D013058:Mass Spectrometry; D051379:Mice; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013098:Xylariales / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones
keywords: N-oxide; Xylaria longipes; difloxacin; enrofloxacin; marbofloxacin