METABOLITE REVERSAL OF ANTIBIOTIC INHIBITION, ESPECIALLY REVERSAL OF AUREOMYCIN INHIBITION BY RIBOFLAVIN

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Abstract
Numerous pure metabolites reverse the inhibition of growth of Escherichia coli, strain B, caused by certain levels of penicillin G, aureomycin, dihydrostreptomycin, terramycin, or chloramphenicol. The tests were conduced by the spread plate method in glucose-salts agar using about 100 washed cells as inoculum. The best reversal was obtained in the case of aureomycin. Riboflavin, lumichrome, inosine and glycine were superior reversing metabolites of aureomycin in 12 different bacteria. Concn. expts. with riboflavin indicate the aureomycin-riboflavin relationship is competitive. Aureomycin competitively inhibited utilization of riboflavin by a riboflavin-less mutant of Bacillus subtilis. Dichlorodiaminobenzene, a known inhibitor of riboflavin synthesis, aureomycin and terramycin all were found to inhibit riboflavin synthesis in the test bacteria. In the presence of a subinhibitory level of dichlorodiaminobenzene only 1/16 as much aureomycin was required to inhibit B. subtilis, strain ATCC 6633, as was required in the absence of the analog. The concept of protected inhibition is developed and proposed as the mechanism of the observed potentiation, and its general significance is discussed.