MODE OF ACTION OF TRICHOMYCIN

I. EFFECT OF TRICHOMYCIN ON THE CARBOHYDRATE RESPIRATION OF CANDIDA ALBICANS

Abstract

The mode of antimicrobial action of trichomycin on C. albicans was investigated from the biochemical standpoint. The first step of the investigation involved an inquiry into the effect of trichomycin on carbohydrate respiration by C. albicans.
Trichomycin inhibited not only the oxidation of glucose but also that of several other carbohydrates in concentrations lower than the minimum amount required to inhibit the growth of C. albicans completely. Therefore, the inhibitory action on respiration was considered as being primary for the mode of action of the drug. However, these inhibitory effects on the carbohydrate respiration decreased with the lapse of reaction time. Accordingly, it was considered that the inhibitory effects progressed reversibly and were lacking in the specificity for oxidation substrate. In regards to the mechanism by which the aerobic carbohydrate dissimilation was inhibited by trichomycin, it was supposed that the drug might inhibit the condensation of pyruvate and oxalacetate. This reaction is the first step in the oxidation of carbohydrates and the intercept of the first half of the reactive process in the tricarboxylic acid cycle. Furthermore, trichomycin exerted a strong inhibitory effect upon the adaptive oxidation of sucrose which was decomposed after a long lag period. Finally, it was considered that the drug might also prevent the adaptive process.
However, as for the mode of inhibitory action on respiration, several possible explanations may come into existence. For this reason the present study should be reconsidered after further investigation is made on the effects of trichomycin on other metabolic pattern concerned with C. albicans.