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Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13594-9. doi: 10.1073/pnas.1305982110. Epub 2013 Jul 31.

Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis.

Author information

1
Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Abstract

Infection by pathogenic fungi, such as Candida albicans, begins with adhesion to host cells or implanted medical devices followed by biofilm formation. By high-throughput phenotypic screening of small molecules, we identified compounds that inhibit adhesion of C. albicans to polystyrene. Our lead candidate compound also inhibits binding of C. albicans to cultured human epithelial cells, the yeast-to-hyphal morphological transition, induction of the hyphal-specific HWP1 promoter, biofilm formation on silicone elastomers, and pathogenesis in a nematode infection model as well as alters fungal morphology in a mouse mucosal infection assay. We term this compound filastatin based on its strong inhibition of filamentation, and we use chemical genetic experiments to show that it acts downstream of multiple signaling pathways. These studies show that high-throughput functional assays targeting fungal adhesion can provide chemical probes for study of multiple aspects of fungal pathogenesis.

KEYWORDS:

fungal pathogens; hyphal morphogenesis; small molecule screening

PMID:
23904484
PMCID:
PMC3746938
DOI:
10.1073/pnas.1305982110
[Indexed for MEDLINE]
Free PMC Article

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