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.
journal_name
Proc Natl Acad Sci U S Aauthors
Uchida M,McDermott G,Wetzler M,Le Gros MA,Myllys M,Knoechel C,Barron AE,Larabell CAdoi
10.1073/pnas.0906145106subject
Has Abstractpub_date
2009-11-17 00:00:00pages
19375-80issue
46eissn
0027-8424issn
1091-6490pii
0906145106journal_volume
106pub_type
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