An amine ed formed by bacteria during sulfonamide bacteriostasis.

When Escherichia coli was grown in a synthetic medium containing salts, amino acids, and glucose in the presence of bacteriostatic concentrations of sulfonamides, an increase in total diasotizable amine was noted (1). This has nolv been found to be due to the production of a new heterocyclic amine, the nature of mhich may ultimately throIv light on the mechanism of sulfonamide bacteriost,asis. The formation of the amine is not limited to one kind of bacterium nor to any specific sulfonamide drug. It lvas noted with a number of different organisms (Table I). Each of the drugs tried, sulfanilamide, sulfadiazine, sulfapyridine, and sulfathiazole, xvas found to be effective, but the actual amount formed varied xvith the concentration and nature of the drug. From the figures in Table II it is seen that the amount of nelv amine formed Tvas not proportional to the amount of drug used, but the quantity formed was ahvays of the same order of magnitude lvhen bacteriostatic concentrations of different drugs were used. Since the rat,io of amine formed to drug used Was greatest xvith sulfadiazine, this drug lvas selected for preparation of the material for isolation. p-Aminobenzoic acid, in concentrations sufficient to block the action of the sulfonamides, prevented the formation of the amine. None of the amine ‘vvas formed in the absence of sulfonamides or lvhen atabrine, plasmochin, or penicillin Tvas used in concentrations sufficient to inhibit the growth of the bacteria. The cultures used for chemical studies and for isolation were chiefly those of Escherichia coli lvith 0.5 mg. per cent of sulfadiazine as the bacteriostatic agent. The nelvly formed amine, in contrast to sulfonamides, mas not acetylated in neutral aqueous solution by acetic anhydride. It could thus be distinguished conveniently and quantitatively from the sulfonamide in solutions containing both of the amines. Quantitative measurements of diazotizable amine by the Bratton-Marshall method for sulfonamide analysis (2) shelved that the total amount after incubation was equal to