Biotransformation of ciprofloxacin by Xylaria longipes: structure elucidation and residual antibacterial activity of metabolites
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The impressive ability of the fungus Xylaria longipes to transform the highly persistent fluoroquinolone ciprofloxacin into microbiologically less active degradation products was demonstrated. Fluoroquinolones are used extensively in both human and veterinary medicine. Poor metabolization and high chemical stability of these synthetic antibiotics led to their presence in several environmental compartments. This undesirable behavior may promote the spread of resistance mechanisms due to concomitant exposure to bacteria. Therefore, the biotransformation of ciprofloxacin, one of the most prescribed fluoroquinolones in human medicine, by the ascomycetous soft rot fungus X. longipes was investigated in detail. Submerged cultivation of the fungus allowed for high-yield formation of four biotransformation products. These compounds were subsequently purified by preparative high-performance liquid chromatography. Applying accurate mass spectrometry and nuclear magnetic resonance spectroscopy, desethylene-ciprofloxacin, desethylene-N-acetyl-ciprofloxacin, N-formyl-ciprofloxacin and N-acetyl-ciprofloxacin were unambiguously identified. N-acetylation and N-formylation of the drug led to a 75–88% reduction of the initial antibacterial activity, whereas a breakdown of the piperazine substituent resulted in almost inactive products. These findings suggest an important role in the inactivation and degradation of this and other synthetic compounds in the environment.
KeywordsFluoroquinolone Fungus Soft rot Metabolism Mass spectrometry NMR
The authors thank Heike Hausmann, Anja Platt, and Anika Bernhardt (all Justus Liebig University Giessen) for excellent assistance with the NMR analyses. The authors also thank AiM GmbH (Munich, Germany) for kindly providing the BRT MRL screening tests kits for this study.
The authors are grateful to the Deutsche Forschungsgemeinschaft (DFG) and the State of Hesse for funding the TripleTOF mass spectrometer (INST 162/490-1 FUGG). A.S. is supported by the German Federal Environmental Foundation (DBU, grant 31812-01).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
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