Accumulation of KRM-1648 by Mycobacterium aurum and Mycobacterium tuberculosis

Abstract

After exposure to 2 mg/L 14C-labelled KRM-1648 (a new broad-spectrum benzoxazinorifamycin antibiotic) for 5 min, a steady-state concentration of 31.3 ± 3 ng/mg cells KRM-1648 and 12.6 ± 0.3 ng/mg cells KRM-1648 was accumulated by wild-type antibiotic-susceptible Mycobacterium aurum (A+) and Mycobacterium tuberculosis (H37Rv), respectively. However, 2 mg/L KRM-1648 was bactericidal for M. tuberculosis. A steady-state concentration of 3.7 ± 0.1 ng/mg cells KRM-1648 was accumulated after exposure to 0.5 mg/L. At pH 4 higher concentrations were accumulated than at pH 7. A sub-inhibitory concentration of ethambutol increased the concentration of KRM-1648 accumulated, but Tween 80 and reserpine had little or no effect.