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SUMMARY: The sensitivity of 4 strains of Escherichia coli and of Aerobacter aero- genes when growing under aerobic and under anaerobic conditions in heavily buffered enriched medium was compared. Each comparison covered a series of pH values from 5-5 to 8.0. A distinct pattern emerged for each group of organisms and this would appear to be related to the enzymic make-up of the organism with respect to carbohydrate metabolism and not to the pH developed in the medium during growth or to the growth rate of the organism. Comparison of the behaviour of A. aerogenes under identical conditions, but in a simple medium, suggests that dihydrostrepto- mycin is more effective against synthesizing than against energy-producing mechanisms. The activity of streptomycin and dihydrostreptomycin is decreased under anaerobic conditions (Bondi, Dietz & Spaulding, 1946; Geiger, Green & Waks- man, 1946; Hurowitz, Rosano, Blattberg & Rosenfeld, 1955; Williamson & White, 1956). Three suggestions have been advanced to explain this pheno- menon. First, an altered environment, the direct effect of the incomplete catabolism of metabolites. This gives rise to acidic end-products, lowering the pH of the medium and thereby decreasing the effective concentration of the antibiotic (Geiger et al. 1946). Secondly, a slower rate of growth, for it has been stated that the faster an organism grows the greater its sensitivity; indeed there would appear to be a direct relationship (Hurowitz et al. 1955). Finally, 'the antibacterial action of streptomycin may be due to its ability to block some enzyme system, oxidative in nature, which is essential only to the growth of susceptible aerobic bacteria, an enzyme system which anaerobes do not possess ' (Bondi et al. 1946). This idea could conceivably apply to facultative anaerobes if their functional enzymic pattern varies with the oxygen content of their environment. Of the many metabolic pathways that may be affected by streptomycin those concerned with carbohydrate breakdown have been most fully investigated. Interference with the aerobic metabolism of pyru- vate by Escherichia coli was reported by Oginsky, Smith & Umbreit (1949) and that of anaerobic dissimilation by Barkulis (1953). I The several path- ways for the breakdown of pyruvate by E. coli and Aerobacter aerogenes are the same with the exception of that leading to the formation of acetylmethyl- carbinol by A, aerogenes. Furthermore, this mechanism functions under both aerobic and anaerobic conditions. It was thought that by working under carefully controlled environmental conditions with organisms whose growth rate and general metabolic behaviour was known, some reason for the greater resistance to dihydrostreptomycin of a facultative anaerobe when growing anaerobically might be forthcoming.

Dihydrostreptomycin and Anaerobiosis--Indirect Evidence for Two Sites of Action of Dihydrostreptomycin