STUDIES ON T H E ANTIBACTERIAL ACTION OF T H E SULFONAMIDE DRUGS I. TI-IE RELATION 0]? p-AMINOBENZOIC ACID TO THE MECt~XNISM 0~" BACTERIOSTASIS* BY W. BARRY

The mechanism whereby sulfanilamide and its derivatives prevent bacterial growth is not known. None of the various theories advanced (1-3) has been conclusively substantiated by direct experimental proof. The most important recent contribution to the problem has been that of Woods (4), who demonstrated that p-aminobenzoic acid "blocks" the bacteriostatic effect of sulfanilamide in vitro. Following the isolation by Stamp (5) and Green (6) of bacterial extracts which antagonize the action of sulfanilamide, Woods obtained from yeast a potent antisuLfanilamide factor which appeared to have chemical properties similar to p-aminobenzoic acid but which could not be definitely identified as such. p-Aminobenzoic acid itself was found to annul the bacteriostatic effect of sulfanilamide, and Woods predicted that this simple organic acid would eventually l:e shown to be a metabolite essential for bacterial growth3 He also formulated the theory that sulfanilamide causes bacteriostasis by inhibiting specifically the enzymatic reaction involved in the utilization of p-aminobenzoic acid and attributed the inhibition of this reaction to the chemical similarity of the drug and the essential metabolite. Important evidence supporting Woods' hypothesis was published in the same year by Rubbo and Gillespie (8). They reported the chemical isolation from