title: Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in Candida albicans.
abstract: The opportunistic pathogen Candida albicans can undergo phenotypic switching between a benign, unicellular phenotype and an invasive, multicellular form that causes candidiasis. Increasingly, strains of Candida are becoming resistant to antifungal drugs, making the treatment of candidiasis difficult, especially in immunocompromised or critically ill patients. Consequently, there is a pressing need to develop new drugs that circumvent fungal drug-resistance mechanisms. In this work we used soft X-ray tomography to image the subcellular changes that occur as a consequence of both phenotypic switching and of treating C. albicans with antifungal peptoids, a class of candidate therapeutics unaffected by drug resistance mechanisms. Peptoid treatment suppressed formation of the pathogenic hyphal phenotype and resulted in striking changes in cell and organelle morphology, most dramatically in the nucleus and nucleolus, and in the number, size, and location of lipidic bodies. In particular, peptoid treatment was seen to cause the inclusion of lipidic bodies into the nucleus.
authors.affiliation: Department of Anatomy, School of Medicine, University of California, San Francisco, CA, USA.
authors.forename: Maho
authors.initials: M
authors.lastname: Uchida
authors.forename: Gerry
authors.initials: G
authors.lastname: McDermott
authors.forename: Modi
authors.initials: M
authors.lastname: Wetzler
authors.forename: Mark A
authors.initials: MA
authors.lastname: Le Gros
authors.forename: Markko
authors.initials: M
authors.lastname: Myllys
authors.forename: Christian
authors.initials: C
authors.lastname: Knoechel
authors.forename: Annelise E
authors.initials: AE
authors.lastname: Barron
authors.forename: Carolyn A
authors.initials: CA
authors.lastname: Larabell
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000648:ultrastructure*; D025141:Drug Resistance, Fungal; D025301:Hyphae / Q000187:drug effects / Q000648:ultrastructure*; D034444:Peptoids / Q000494:pharmacology*; D010641:Phenotype
chemical_list: D000935:Antifungal Agents; D034444:Peptoids