Soft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in Candida albicans

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TitleSoft X-ray tomography of phenotypic switching and the cellular response to antifungal peptoids in Candida albicans
Publication TypeJournal Article
Year of Publication2009
AuthorsUchida M, McDermott G, Wetzler M, Le Gros MA, Myllys M, Knoechel C, Barron AE, Larabell CA
Journal TitleProceedings of the National Academy of Sciences of the United States of America
Volume106
Pages19375-19380
Journal DateNov 17
ISBN Number0027-8424
Accession NumberISI:000271907400029
Keywordsantimicrobial peptides, Cells, drug discovery, epidemiology, fungal-infections, Microscopy, nucleolus, resistance, saccharomyces-cerevisiae, spatial-resolution
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.

URL<Go to ISI>://000271907400029