Reversal of aureomycin inhibition of bacterial cell-free nitro reductase by manganese.

Previous publications from this laboratory (1, 2) showed that Aureomycinl in low concentrations inhibited the formation of the corresponding arylamines from chloramphenicol’ and p-nitrobenzoic acid. The enzyme system which mediated these reductions was complex. A dicarboxylic acid (e.g. I-malic) served as the hydrogen donor and the hydrogen was transported via diphosphopyridine nucleotide. In addition, L-cysteine was essential. It was tentatively concluded that Aureomycin inhibition of the reaction sequence occurred prior to the formation of dihydrodiphosphopyridine nucleotide. Van Meter and Oleson (3), working with preparations of liver mitochondria, confirmed the report of Loomis (4) that Aureomycin inhibited oxidative phosphorylation. Van Meter et al. further showed that the addition of magnesium ion reversed the inhibition of respiration by Aureomycin (5). Albert (6) has reported that Aureomycin and Terramycin chelate with various cations and Soncin (7) has recently reported that Mg++ reverses the antibiotic activity of Aureomycin and Terramycin. It is the purpose of the present communication to report on additional experiments which indicate that Aureomycin inhibits nitro reduction by inhibiting the formation of reduced DPN from DPN2 and I-malate. As measured spectrophotometrically, certain cations are essential for the formation of reduced DPN from DPN and Z-malate and are markedly stimulatory for the formation of arylamine from chloramphenicol or p-nitrobenzoic acid. The experiments reported herein suggest that in this reduction Aureomycin inhibits by virtue of its ability to chelate or combine with cations.