Enhancement of the fungicidal activity of amphotericin B by allicin: effects on intracellular ergosterol trafficking.
In Saccharomyces cerevisiae, ergosterol was visible in the plasma membrane of untreated cells and was enriched in the vacuole membrane in response to amphotericin B (AmB) treatment at a non-lethal concentration. The simultaneous addition of allicin was inhibitory to AmB-induced ergosterol enrichment in the vacuole membrane, resulting in increased sensitivity of the organelles to the disruptive action of AmB. Allicin was also inhibitory to ergosterol enrichment in the vacuole membrane that was achieved by its external addition to cells. The combined fungicidal activity of AmB and allicin was suppressed together with suppression of vacuole membrane damage in cells where ergosterol had been fully enriched in the vacuole membrane. AmB caused direct disruptive damage of the isolated vacuoles, but the antibiotic was apparently less effective in disrupting the organelles that were isolated after ergosterol enrichment. These findings suggest that allicin enhances AmB-induced vacuole membrane damage by inhibiting ergosterol trafficking from the plasma membrane to the vacuole membrane.
Ogita
Akira
A
Research Center for Urban Health and Sports, Osaka City University, Osaka, Japan.
Fujita
Ken-Ichi
K
Tanaka
Toshio
T
D000666:Amphotericin B / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides; D004875:Ergosterol / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005737:Garlic; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D013441:Sulfinic Acids / Q000494:pharmacology*; D014617:Vacuoles / Q000187:drug effects
D000935:Antifungal Agents; D004220:Disulfides; D010936:Plant Extracts; D013441:Sulfinic Acids; C006452:allicin; D000666:Amphotericin B; D004875:Ergosterol