title: 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-C₃(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-C₃(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.
authors.affiliation: Charles University, Faculty of Mathematics and Physics, Institute of Physics, Prague, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Kodedová
authors.forename: Karel
authors.initials: K
authors.lastname: Sigler
authors.forename: Bernard D
authors.initials: BD
authors.lastname: Lemire
authors.forename: Dana
authors.initials: D
authors.lastname: Gášková
mesh_terms: D000666:Amphotericin B / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D001548:Benzalkonium Compounds / Q000737:chemistry / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D007097:Imines; D007700:Kinetics; D008826:Microbial Sensitivity Tests / Q000379:methods*; D009761:Nystatin / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000187:drug effects* / Q000235:genetics; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D001548:Benzalkonium Compounds; D007097:Imines; D011725:Pyridines; D013501:Surface-Active Agents; D009761:Nystatin; D012967:Sodium Dodecyl Sulfate; D000666:Amphotericin B; C034213:octenidine