STUDIES ON THE ANTIBACTERIAL ACTION OF THE SULFONAMIDE DRUGS : I. THE RELATION OFp-AMINOBENZOIC ACID TO THE MECHANISM OF BACTERIOSTASIS

The following observations have been made which substantiate the theory that the sulfonamide drugs used in the treatment of bacterial infections exert their bacteriostatic effect by competing with the essential metabolite, p-amino-benzoic acid, for an important enzyme site on the bacterial cell. 1. p-Aminobenzoic acid was shown to nullify the bacteriostatic effect of all of the six sulfonamide compounds studied even though the drugs exhibited marked differences in chemical structure. 2. The bacteriostatic potency of each sulfonamide drug was found to be directly proportional to its ability to counteract the antibacteriostatic action of p-aminobenzoic acid. 3. In the case of each drug tested over a wide range of concentrations the minimum amount of p-aminobenzoic acid needed to prevent bacteriostasis was such that the ratio of p-aminobenzoic acid to drug was constant. 4. The linear relationship between p-aminobenzoic acid and drug was interpreted as indicating the competitive inhibition of an essential enzyme reaction by a substance chemically related to the substrate. This interpretation was supported by the fact that the equation derived on purely theoretical grounds relating drug and acid expressed the same linear relationship as that observed experimentally.