Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis
Authors
Fazly, AhmedJain, Charu
Dehner, Amie C.
Issi, Luca
Lilly, Elizabeth A.
Ali, Akbar
Cao, Hong
Fidel, Paul L. Jr.
Rao, Reeta P.
Kaufman, Paul D.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologySmall Molecule Screening Facility
Program in Gene Function and Expression
Document Type
Journal ArticlePublication Date
2013-08-13Keywords
Candida albicansCell Adhesion
High-Throughput Screening Assays
Hyphae
Morphogenesis
Piperazines
Small Molecule Libraries
UMCCTS funding
Pathogenic Microbiology
Metadata
Show full item recordAbstract
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.Source
Fazly A, Jain C, Dehner AC, Issi L, Lilly EA, Ali A, Cao H, Fidel PL Jr, Rao RP, Kaufman PD. Chemical screening identifies filastatin, a small molecule inhibitor of Candida albicans adhesion, morphogenesis, and pathogenesis. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13594-9. doi:10.1073/pnas.1305982110.Link to article on publisher's site
DOI
10.1073/pnas.1305982110Permanent Link to this Item
http://hdl.handle.net/20.500.14038/44016PubMed ID
23904484Related Resources
ae974a485f413a2113503eed53cd6c53
10.1073/pnas.1305982110