title: Synergistic fungicidal activity of Cu(2+) and allicin, an allyl sulfur compound from garlic, and its relation to the role of alkyl hydroperoxide reductase 1 as a cell surface defense in Saccharomyces cerevisiae.
abstract: Cu(2+) showed a dose-dependent fungicidal activity against Saccharomyces cerevisiae cells, and its lethal effect was extremely enhanced in the presence of allicin, an allyl sulfur compound from garlic. The fungicidal activity of Cu(2+) was unaffected or rather attenuated by other sulfur-containing compounds such as N-acetyl-cysteine, l-cysteine or dithiothreitol. Ca(2+) could absolutely protect against the lethal effect of Cu(2+) itself, but showed no protection against the fungicidal activity of Cu(2+) newly generated in combination with allicin. Cu(2+) accelerated an endogenous generation of reactive oxygen species (ROS) in S. cerevisiae cells at a lethal concentration, but such intracellular oxidative stress induction was not observed during cell death progression upon treatment with Cu(2+) and allicin. A surfactant, sodium N-lauroyl sarcosinate (SLS), enhanced the solubilization of a few proteins including alkyl hydroperoxide reductase 1 (AHP1) in intact cells, accounting for the absence of this protein in the extract from allicin-treated cells. Allicin-treated cells were rendered extremely sensitive to the subsequent Cu(2+) treatment as in the case of SLS-treated cells. Allicin-treated cells and SLS-treated cells similarly showed an increased sensitivity to exogenously added tert-butyl hydroperoxide (t-BOOH), an organic peroxide that is detoxified by the action of AHP1. Our study suggests that allicin influences the mode of cell surface localization or the related function of AHP1 as a defense against phospholipid peroxidation by the external action of Cu(2+).
authors.affiliation: Institute for Health and Sport Sciences, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ogita
authors.forename: Kiyoo
authors.initials: K
authors.lastname: Hirooka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsutsui
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Fujita
authors.forename: Makoto
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Toshio
authors.initials: T
authors.lastname: Tanaka
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002473:Cell Wall / Q000187:drug effects* / Q000201:enzymology; D003300:Copper / Q000494:pharmacology*; D003902:Detergents / Q000494:pharmacology; D004220:Disulfides; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D017382:Reactive Oxygen Species; D012441:Saccharomyces cerevisiae / Q000187:drug effects*; D012521:Sarcosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013441:Sulfinic Acids / Q000494:pharmacology*
chemical_list: C515936:AHP1 protein, S cerevisiae; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D003902:Detergents; D004220:Disulfides; D017382:Reactive Oxygen Species; D013441:Sulfinic Acids; C006452:allicin; C025231:sarkosyl; D003300:Copper; D010544:Peroxidases; D054464:Peroxiredoxins; D012521:Sarcosine