Growth Inhibition of Tubercle Bacilli by Analogues of Phenylalanine.

Many studies have been devoted to the inhibitory action of various metabolite analogues on microbial growth. In most of this work, however, such nonpathogens as the yeasts, lactobacilli, and Escherichia coli have served as the test organism and there has been little attempt to correlate or extend the studies to pathogenic bacteria, especially those organisms synthesizing their own growth factors. In a recent study we have shown the results obtained when 96 metabolite antagonists were tested on two virulent strains of the tubercle bacillus, an organism capable of synthesizing its own vitamins (Pope and Smith, 1949). Analogues of biotin and p-minobenzoic acid were found to exert a specific bacteriostatic action on the organism, and Drea (1948) has found that an analogue of phenylalanine, ,8-2-thienylalanine, is inhibitory for the tubercle bacillus at high concentrations. With such findings as evidence that an inhibition of synthesis or utilization of a metabolite may be produced in a pathogenic organism that has the inherent ability to synthesize its own vitamins and amino acids from simple substances contained in the culture medium, further studies of this kind are indicated. The present paper reports the inhibition of growth of the tubercle bacillus by five analogues of phenylalanine and the effect of phenylalanine on this inhibition. The compounds studied were ,3-2-thienylalanine, fB-3-thienylalanine, j%2-furylalanine, a-amino-phenylmethane sulfonic acid, and ,B-hydroxyphenylalanine.