INHIBITION OF NONFOLIC-ACID-REQUIRING ORGANISMS BY FOLIC ACID ANTAGONISTS: MECHANISM OF REVERSAL

Abstract

Although folic acid antagonists have been reported to be unable to inhibit nonfolic-acid-requiring organisms, it was found that several such antagonists were quite active inhibitors of Lactobacillus arabinosus and several species of yeasts when grown in minimal media. The growth inhibition produced under these circumstances was not reversed by compounds related to folic acid but was reversed by thiamine and vitamin B6compounds. A rapidly developing physiological adaptation caused by the presence of thiamine and vitamin B6apparently was the mechanism by which these organisms overcame the inhibitory effects of folic acid antagonists. 6-Mercaptopurine antagonized this reversal and thus was strongly synergistic with folic acid analogues under certain conditions.