title: Accumulation of KRM-1648 by Mycobacterium aurum and Mycobacterium tuberculosis.
abstract: After exposure to 2 mg/L (14)C-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.
authors.affiliation: Antimicrobial Agents Research Group, Division of Immunity and Infection, The Medical School, University of Birmingham, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK. l.j.v.piddock@bham.ac.uk
authors.forename: L J
authors.initials: LJ
authors.lastname: Piddock
authors.forename: V
authors.initials: V
authors.lastname: Ricci
mesh_terms: D000904:Antibiotics, Antitubercular / Q000378:metabolism* / Q000494:pharmacology; D002250:Carbon Radioisotopes / Q000378:metabolism; D015169:Colony Count, Microbial; D004977:Ethambutol / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D011136:Polysorbates; D012110:Reserpine / Q000494:pharmacology; D012294:Rifamycins / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000904:Antibiotics, Antitubercular; D002250:Carbon Radioisotopes; D011136:Polysorbates; D012294:Rifamycins; C068980:KRM 1648; D012110:Reserpine; D004977:Ethambutol