Further Studies on Potentiation of Inhibitor Action Through Determination of Reversing Metabolites

Abstract

Pittillo and Foster (1954) demonstrated that it is possible on a rational basis to formulate synergistic combinations of inhibitors for any particular bacterium. Prediction of combinations of inhibitors which are apt to be synergistic depends upon knowledge that the suppression of bacterial growth caused by individual inhibitors can be reversed by corresponding essential

Investigation of (S)-(−)-Acidomycin: A Selective Antimycobacterial Natural Product That Inhibits Biotin Synthase

“…Acidomycin ( 11 , ACM, also known as actithiazic acid, cinnamonin, and mycobacidin) was discovered in 1952 independently by four different research teams − and was originally isolated from culture filtrates of Streptomyces virginiae , Streptomyces acidomyceticus , Streptomyces lavendulae , and Streptomyces cinnamonensis . , Acidomycin possessed a considerable degree of selective antimicrobial activity against M. tuberculosis in vitro but was inactive against an M. tuberculosis infection in vivo . , The inhibitory activity of acidomycin depended on the incubation period, amount of inoculum, and concentration of biotin in the medium . Concentrations of acidomycin ranging from 0.25 to 10 μg/mL (1.2–46.0 μM) were required to inhibit the growth of mycobacteria in vitro , and conversely, acidomycin did not inhibit the growth of certain Gram-positive and Gram-negative bacteria or fungi at concentrations as high as 1 mg/mL (4.6 mM). , The presence of biotin in growth media as low as 0.064 μg/mL (0.26 μM) was shown to fully antagonize the antibiotic activity of acidomycin and was attributed to the structural similarity between acidomycin and biotin. ,,,− Dethiobiotin (DTB, 4 ) also affected the inhibitory of acidomycin, albeit to a much lesser degree . Taken together, these data implicated acidomycin as an inhibitor of the biotin biosynthetic pathway.…”