title: Inactivation of kanamycin A by phosphorylation in pathogenic Nocardia.
abstract: Among the five species of pathogenic Nocardia, i.e., N. asteroides, N. brasiliensis, N. farcinica, N. nova and N. otitidiscaviarum, all strains of N. brasiliensis and N. farcinica showed resistance to an aminoglycoside antibiotic, kanamycin A, showing the MIC (minimum inhibitory concentration) values of more than 100 micrograms/ml. This species-specific difference in sensitivity was found to be explained by the production of an inactivation enzyme, aminoglycoside 3'-phosphotransferase APH(3'). Structural studies by mass and NMR spectroscopy on the inactivated substance produced by a cell-free extract of the Nocardia confirmed the conversion of kanamycin A to an inactive substance, kanamycin A 3'-phosphate. The MIC values of N. otitidiscaviarum and N. nova for kanamycin A, on the other hand, ranged from 0.78 micrograms/ml to 100 micrograms/ml, and both species were non-producers of APH(3'). Sensitivity to the antibiotic and APH(3') productivity of N. asteroides varied depending on the strain.
authors.affiliation: Department of Experimental Chemotherapy, Chiba University.
authors.forename: K
authors.initials: K
authors.lastname: Yazawa
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
authors.forename: A
authors.initials: A
authors.lastname: Maeda
authors.forename: T
authors.initials: T
authors.lastname: Kudo
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: N
authors.initials: N
authors.lastname: Saito
authors.forename: A
authors.initials: A
authors.lastname: Kubo
mesh_terms: D002240:Carbohydrate Sequence; D004789:Enzyme Activation; D007612:Kanamycin / Q000378:metabolism*; D019868:Kanamycin Kinase; D007613:Kanamycin Resistance; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009615:Nocardia / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D007612:Kanamycin; D010770:Phosphotransferases; D019868:Kanamycin Kinase