MICROBIAL MODELS OF SOIL METABOLISM - BIOTRANSFORMATIONS OF DANOFLOXACIN

Danofloxacin is a new synthetic fluoroquinolone antibacterial agent un der development for exclusive use in veterinary medicine, Such use cou ld lead to deposition of low levels of danofloxacin residues in the en vironment in manure from treated livestock, This study was conducted t o evaluate the potential for indigenous soil microorganisms to metabol ize danofloxacin, Cultures of 72 soil microorganisms representing a di verse panel of bacteria, fungi and yeast were incubated with danofloxa cin mesylate substrate and samples analyzed periodically by high perfo rmance liquid chromatography for loss of danofloxacin and formation of metabolites, Some samples were further analyzed by liquid chromatogra phy-mass spectrometry and mass spectrometry to confirm metabolite iden tification, Twelve organisms, representing eight different genera, bio transformed danofloxacin to metabolites detectable by the chromatograp hic methods employed, Two Mycobacterium species, two Pseudomonas speci es, and isolates of Nocardia sp, Rhizopus arrhizus and Streptomyces gr iseus all formed N-desmethyldanofloxacin. The formation of the 7-amino danofloxacin derivative, ro-7-amino-4-oxo-1,4-dihydroquinoline-3-carb oxylic acid by cultures of Candida lipopytica, Pseudomonas fluorescens , two Mycobacterium species and three Penicillium species demonstrates the propensities of these cultures to completely degrade the piperazi ne ring, At least two additional and unidentified metabolite peaks wer e observed in chromatograms of Aspergillus nidulans and Penicillium sp cultures, Radiolabled [2-C-14]danofloxacin added to cultures of the f ungus Curvularia lunata was apparently mineralized, with approximately 31% of the radiolabel recovered as volatile metabolites after 24 h of incubation, indicating the susceptibility of the quinolone ring to mi crobial metabolic degradation.