title: Deletion ofAIF1but not ofYCA1/MCA1protectsSaccharomyces cerevisiaeandCandida albicanscells from caspofungin-induced programmed cell death.
abstract: Caspofungin was the first member of a new class of antifungals called echinocandins to be approved by a drug regulatory authority. Like the other echinocandins, caspofungin blocks the synthesis of β(1,3)-D-glucan of the fungal cell wall by inhibiting the enzyme, β(1,3)-D-glucan synthase. Loss of β(1,3)-D-glucan leads to osmotic instability and cell death. However, the precise mechanism of cell death associated with the cytotoxicity of caspofungin was unclear. We now provide evidence thatSaccharomyces cerevisiaecells cultured in media containing caspofungin manifest the classical hallmarks of programmed cell death (PCD) in yeast, including the generation of reactive oxygen species (ROS), the fragmentation of mitochondria, and the production of DNA strand breaks. Our data also suggests that deleting AIF1 but not YCA1/MCA1 protectsS. cerevisiaeandCandida albicansfrom caspofungin-induced cell death. This is not only the first time that AIF1 has been specifically tied to cell death inCandidabut also the first time that caspofungin resistance has been linked to the cell death machinery in yeast.
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, U.S.A. ; Current address: University of Massachusetts School of Medicine, 55 Lake Ave. N., Worcester, MA 01655, U.S.A.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chin
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, U.S.A.
authors.forename: Faith
authors.initials: F
authors.lastname: Donaghey
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, U.S.A. ; Current address: Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115, U.S.A.
authors.forename: Katherine
authors.initials: K
authors.lastname: Helming
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, U.S.A.
authors.forename: Morgan
authors.initials: M
authors.lastname: McCarthy
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, U.S.A.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rogers
authors.affiliation: Department of Biology, Providence College, Providence, RI 02918, U.S.A.
authors.forename: Nicanor
authors.initials: N
authors.lastname: Austriaco
keywords: AIF1; Candida albicans; MCA1/YCA1; Saccharomyces cerevisiae; caspofungin; programmed cell death