Biotransformation of ciprofloxacin by Xylaria longipes: structure elucidation and residual antibacterial activity of metabolites

• Published in: Applied microbiology and biotechnology Vol. 102; no. 19; pp. 8573 - 8584
• Main Authors: Rusch, Marina, Spielmeyer, Astrid, Zorn, Holger, Hamscher, Gerd
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2018; Springer; Springer Nature B.V
• Subjects: Acetylation; Antibacterial activity; Antibiotics; Biodegradation; Biomedical and Life Sciences; Biotechnology; Biotransformation; Ciprofloxacin; Cultivation; Deactivation; Degradation; Degradation products; Dosage and administration; Ecology; Environmental Biotechnology; Fluoroquinolones; Fungi; Fungiculture; High performance liquid chromatography; Inactivation; Life Sciences; Liquid chromatography; Magnetic resonance spectroscopy; Mass spectrometry; Mass spectroscopy; Medicine; Metabolites; Microbial Genetics and Genomics; Microbiology; NMR; Nuclear magnetic resonance; Organic chemistry; Piperazine; Soft rot; Veterinary medicine; Fungus; NMR; Fluoroquinolone; Metabolism; Mass spectrometry; Soft rot
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-018-9231-y

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.