Inhibition of Bacteriostatic Action of Sulfanilamide by Yeast Extracts

Substances capable of preventing the bacteriostatic action of sulfanilamide have been found widely distributed in nature. Woods reported that a substance was present in an extract prepared from Baker's yeast which lessened the inhibitory effect which sulfanilamide has upon the growth of Streptococcus hemolyticus. Further experiments upon the properties of this compound led him to the conclusion that it resembled p-aminobenzoic acid, and investigations of preparations of that substance in pure solution showed that it markedly inhibited the anti-bacterial action of sulfanilamide. Since this paper was published, Rubbo and Gillespie have isolated p-aminobenzoic acid as the benzoyl derivative from a Brewer's yeast extract. In vivo, p-aminobenzoic acid prevents the favorable action of sulfanilamide upon experimental infections with streptococci and pneumococci as shown by Selbie and McCarty. Woods found that his extracts contained, in addition to the anti-sulfanilamide factor, a compound which promoted the growth of the organisms studied. This substance was present in small amounts because after dilution of these extracts its presence could no longer be demonstrated, although the anti-sulfanilamide action could still be shown. It is generally agreed that the bacteriostatic action of sulfanilamide is influenced by the composition of the culture medium, particularly by peptone and other growth-promoting factors. Therefore, at the present time anti-sulfanilamide activity appears to be due to (a) factors that are favorable to the growth of the organisms and (b) compounds that specifically interfere with the action of sulfanilamide. In this paper experiments designed to extend further the study of anti-sulfanilamide activity of yeast extracts are reported. Attempts were made to prepare extracts from Baker's yeast in which substances favoring the growth of organisms would be absent. A fat-free, protein and peptone-free, extract from Baker's yeast was made by a technic similar to that developed by Stamp and Woods. Eight different samples of yeast were used, each weighing approximately 250 g. The procedure involved extraction with ammonia, precipitation with phosphotungstic acid, removal of excess phosphotungstic acid with barium hydroxide, and concentration at reduced pressure at a pH of approximately 7.0.