Abstract
Growth-inhibitory and membrane-damaging effects of terbinafine on Sporothrix schenckii were compared between the wild strains sensitive to terbinafine and tolciclate and the mutant strains tolerant to tolciclate.
The tolciclate-resistant mutant strains were in two types, one lacking squalene epoxidase activity and the other not, and both cross-resistant to terbinafine and naftifine, when referring to concentration for 50% growth inhibition.
Sensitivity to membrane-damaging action by terbinafine of each of the types was compared with that of the wild type by measuring extracellular release levels of K+ and inorganic phosphate. The squalene epoxidase-deficient type showed a slight decrease of sensitivity, while the nondeficient type showed a marked decrease.
These findings suggest that (1) squalene epoxidation is primarily associated with antifungal activity of both terbinafine and tolciclate, and that (2) direct membrane-damaging action is also responsible for the antifungal action at higher concentration of the drugs in fungal such as S. schenckii which are highly sensitive to terbinafine.
