Fluorescence method for determining the mechanism and speed of action of surface-active drugs on yeast cells
Abstract
New antifungal agents are needed to treat life-threatening fungal infections, particularly with the development of resistance. Surface-active antifungals have the advantages of minimizing host toxicity and the emergence of drug resistance.
We have developed a time-dependent drug exposure assay that allows us to rapidly investigate the mechanism of surface-active antifungal drug action. The assay uses a multidrug pump-deficient strain of Saccharomyces cerevisiae and the potentiometric dye 3,3''-dipropylthiacarbocyanine iodide [diS-C(3)(3)] and can assess whether cells are depolarized, hyperpolarized, or permeabilized by drug exposure.
In this work, we investigated the mechanisms of action of five surface-active compounds: SDS, nystatin, amphotericin B, octenidine dihydrochloride, and benzalkonium chloride. The diS-C(3)(3) time-dependent drug exposure assay can be used to identify the mechanisms of action of a wide range of drugs.
It is a fast and cost-effective method for screening drugs to determine their lowest effective concentrations.