Broad long-term objectives: The broad long-term objectives of this work are to identify (i) novel antifungal drug targets and (ii) inhibitors of these antifungal drug targets.
Specific Aims :
Specific Aim 1 of this work is to identify mutants in fungal-specific amino acid and vitamin pathways that undergo nutrient-specific cidal starvation and/or are highly deleterious due to the accumulation of toxic intermediates.
Specific Aim 2 will involve the construction and characterization of the corresponding mutants in C. albicans and C. neoformans. ? ? Relevance: Because there are relatively few antifungal drugs and because of the side effect profiles / efficacy of the available antifungal drugs, there is a great need for novel antifungal drugs. The health relatedness of this project lies in the genetic identification of novel antifungal drug targets. Because the targets will be in fungal-specific pathways, inhibitors should have minimal side effects. Because inhibition of the targets will result in the accumulation of toxic intermediates in the fungus, inhibitors should be effective antifungal drugs. ? ? Relevance of this research to public health: The public health relevance of this work is in its focus on the identification of novel antifungal drug targets that are fungicidal. The identification of fungicidal antifungal drugs, which is a long-term goal, will greatly improve human health. ? ? ?
| Kingsbury, Joanne M; McCusker, John H (2010) Fungal homoserine kinase (thr1Delta) mutants are attenuated in virulence and die rapidly upon threonine starvation and serum incubation. Eukaryot Cell 9:729-37 |
| Kingsbury, Joanne M; McCusker, John H (2010) Cytocidal amino acid starvation of Saccharomyces cerevisiae and Candida albicans acetolactate synthase (ilv2{Delta}) mutants is influenced by the carbon source and rapamycin. Microbiology 156:929-39 |
| Kingsbury, Joanne M; McCusker, John H (2010) Homoserine toxicity in Saccharomyces cerevisiae and Candida albicans homoserine kinase (thr1Delta) mutants. Eukaryot Cell 9:717-28 |
| Kingsbury, Joanne M; McCusker, John H (2008) Threonine biosynthetic genes are essential in Cryptococcus neoformans. Microbiology 154:2767-75 |
