The growth promoting and antisulfonamide activity of pteroylglutamic acid and related compounds for Escherichia coli and Aerobacter aerogenes.

A basis for understanding the mode of action of sulfonamide drugs in terms of the WoodsFildes theory of antagonism (Woods, 1940; Fildes, 1940) was provided by the elucidation of the structure of folic acid (Stokstad et al., 1946; Angier et al., 1946; Mowat et al., 1948). Since folic acid contains a p-aminobenzoic acid moiety, it was postulated that the structurally similar sulfonamides compete with p-aminobenzoic acid for a site in the folic acid synthesizing system (Jukes and Stokstad, 1948; Hotchkiss, 1948; Woods, 1950). The interaction of the sulfonamides and folic acid has since been studied by a number of workers in terms of the WoodsFildes theory (Woods, 1950; Lampen and Jones, 1946a, b, 1947; Shive and Roberts, 1946). In most of the work on antagonism Lactobacius casei and Streptococ faecalis, strain R, were grown on a complex medium contg, apart from purines and pyrimidines, vitamins of the B complex and a casein hydrolyzate, which contains, in addition to most amino acids, large amounts of glutamic acid and various unidentified degradation products. Since p-aminobenzoic acid is concerned not only with the synthesis of folic acid but also indirectly via folic acid with the synthesis of the purines, thyymine and methionine (Kohn and Harris, 1943; Shive and Roberts, 1946; Snell, 1946), it seemed advisable to the authors to investigate a medium free from possible precursors of folic acid or products of its synthetic enzymatic activity. Any growth in this medium then could be attributed to (1) the synthetic ability of the organism, (2) the addition of an added metabolite, (3) the antagonistic action of various compounds to an inhibitory agent.