title: Acetylation and nitrosation of ciprofloxacin by environmental strains of mycobacteria.
abstract: To determine the ability of environmental bacteria to metabolize the frequently prescribed fluoroquinolone drug ciprofloxacin, eight Mycobacterium spp. cultures were grown for 4 days in a medium containing sorbitol and yeast extract with 100 mg x L(-1) ciprofloxacin. After the cultures had been centrifuged and the supernatants extracted with ethyl acetate, two metabolites were purified by using high-performance liquid chromatography. They were identified with liquid chromatography/electrospray ionization mass spectrometry and proton nuclear magnetic resonance spectroscopy. Ciprofloxacin was transformed to both N-acetylciprofloxacin (2.5%-5.5% of the total peak area at 280 nm) and N-nitrosociprofloxacin (6.0%-8.0% of the peak area) by Mycobacterium gilvum PYR-GCK and Mycobacterium sp. PYR100 but it was transformed only to N-acetylciprofloxacin by Mycobacterium frederiksbergense FAn9, M. gilvum ATCC 43909, M. gilvum BB1, Mycobacterium smegmatis mc2155, Mycobacterium sp. 7E1B1W, and Mycobacterium sp. RJGII-135. The results suggest that biotransformation may serve as a ciprofloxacin resistance mechanism for these bacteria.
authors.affiliation: National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR 72079, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Adjei
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Heinze
authors.forename: Joanna
authors.initials: J
authors.lastname: Deck
authors.forename: James P
authors.initials: JP
authors.lastname: Freeman
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Williams
authors.forename: John B
authors.initials: JB
authors.lastname: Sutherland
mesh_terms: D000107:Acetylation; D000890:Anti-Infective Agents / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002939:Ciprofloxacin / Q000378:metabolism*; D024881:Drug Resistance, Bacterial / Q000502:physiology; D024841:Fluoroquinolones / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D015538:Nitrosation; D009170:Nontuberculous Mycobacteria / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin