Targets, including yap1, for antifungal drug discovery and therapy
AssigneeWorcester Polytechnic Institute
InventorsReeta Prusty Rao, Samuel Michael Politz
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Abstract
The present invention is based on the discovery of a two organism model system that can be used to identify virulence factors. The system is also useful in the process of drug delivery. More specifically, we have established valid fungal infection in caenorhabditis elegans with an invading pathogen, the yeast Saccharomyces cerevisiae. Because both species are genetic model organisms, the assay can be used to identify host and virulence factors involved in such interactions.
Claims24
A co-culture comprising a Caenorhabditis elegans (C. elegans) and a Saccharomyces cerevisiae (S. cerevisiae).
A model system for identifying a host or virulence factor that mediates fungal pathogenesis, the system comprising a C. elegans and a fungal pathogen.
A method of identifying a virulence factor relevant to fungal pathogenesis, the method comprising
- (a) providing a co-culture comprising a C. elegans and a fungal pathogen comprising a mutant gene;
- and
- (b) determining whether the fungal pathogen infects the C. elegans, wherein a lack of infection identifies the protein encoded by the wild type correlate of the mutant gene as a virulence factor.
A method of identifying an antifungal compound, the method comprising:
- (a) providing a co-culture comprising a C. elegans and a fungal pathogen comprising a mutant gene;
- (b) determining whether the fungal pathogen infects the C. elegans, wherein a lack of infection identifies the protein encoded by the wild type correlate of the mutant gene as a virulence factor;
- (c) exposing a wild type fungal pathogen that expresses the virulence factor to a test compound;
- and
- (d) determining whether the test compound inhibits expression of the virulence factor, wherein a decrease in the expression of the virulence factor indicates that the test compound is an antifungal compound.
A method of treating a patient who has, or who is at risk of developing, a fungal infection, the method comprising:
- (a) providing a co-culture comprising a C. elegans and a fungal pathogen comprising a mutant gene;
- (b) determining whether the fungal pathogen infects the C. elegans, wherein a lack of infection identifies the protein encoded by the wild type correlate of the mutant gene as a virulence factor;
- (c) exposing a wild type fungal pathogen that expresses the virulence factor to a test compound;
- (d) determining whether the test compound inhibits expression of the virulence factor, wherein a decrease in the expression of the virulence factor indicates that the test compound is an antifungal compound;
- and
- (e) administering an effective amount of the antifungal compound to the patient.
A method of identifying a host factor that promotes fungal pathogenesis, the method comprising:
- (a) providing a co-culture comprising a C. elegans comprising a mutant gene and a wild type fungal pathogen;
- and
- (b) determining whether the fungal pathogen infects the C. elegans, wherein a lack of infection identifies the protein encoded by the wild type correlate of the mutant gene as a host factor that promotes fungal pathogenesis.
Dependencies are inferred from the claim text.