title: In vitro efficacy of corifungin against Acanthamoeba castellanii trophozoites and cysts.
abstract: Painful blinding keratitis and fatal granulomatous amebic encephalitis are caused by the free-living amebae Acanthamoeba spp. Several prescription eye medications are used to treat Acanthamoeba keratitis, but the infection can be difficult to control because of recurrence of infection. For the treatment of encephalitis, no single drug was found useful, and in spite of the use of a combination of multiple drugs, the mortality rate remains high. Therefore, efficient, novel drugs are urgently needed for the treatment of amebic keratitis and granulomatous amebic encephalitis. In this study, we identified corifungin, a water-soluble polyene macrolide, as amebicidal. In vitro, it was effective against both the trophozoites and the cysts. Transmission electron microscopy of Acanthamoeba castellanii incubated with corifungin showed the presence of swollen mitochondria, electron-dense granules, degeneration of cytoplasm architecture, and loss of nuclear chromatin structure. These changes were followed by lysis of amebae. Corifungin also induced the encystment process of A. castellanii. There were alterations in the cyst cell wall followed by lysis of the cysts. Corifungin is a promising therapeutic option for keratitis and granulomatous amebic encephalitis.
authors.affiliation: Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, California, USA.
authors.forename: Anjan
authors.initials: A
authors.lastname: Debnath
authors.forename: Josefino B
authors.initials: JB
authors.lastname: Tunac
authors.forename: Angélica
authors.initials: A
authors.lastname: Silva-Olivares
authors.forename: Silvia
authors.initials: S
authors.lastname: Galindo-Gómez
authors.forename: Mineko
authors.initials: M
authors.lastname: Shibayama
authors.forename: James H
authors.initials: JH
authors.lastname: McKerrow
mesh_terms: D015823:Acanthamoeba Keratitis / Q000188:drug therapy; D048248:Acanthamoeba castellanii / Q000187:drug effects* / Q000648:ultrastructure; D000563:Amebicides / Q000494:pharmacology*; D000617:Aminoglycosides / Q000494:pharmacology*; D002473:Cell Wall / Q000187:drug effects; D004660:Encephalitis / Q000188:drug therapy / Q000469:parasitology; D066298:In Vitro Techniques; D018942:Macrolides / Q000494:pharmacology*; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects; D053058:Trophozoites / Q000187:drug effects
chemical_list: D000563:Amebicides; D000617:Aminoglycosides; D018942:Macrolides; C580586:corifungin