Background: Many small G-proteins in the Ras superfamily require post-translational modification (prenylation) to allow functional association of the protein to membranes. The Cryptococcus neoformans Ras1 protein controls a signal transduction pathway involved in the ability of this human fungal pathogen to grow at 37••••C and to undergo mating. Prenylation events such as farnesylation and geranyl geranylation might therefore be required for the growth and development of this microorganism. Methods/Results: The FTN2 gene, encoding a protein farnesyl transferase • -chain, was identified in C. neoformans. One FTN2 allele was disrupted in a stable diploid strain background by biolistic transformation and homologous recombination. The FTN2/ftn2 diploid was induced to undergo meiosis, and haploid spores were dissected by micromanipulation. All resulting haploid strains had a wild-type FTN2 allele, supporting our hypothesis that this gene encodes an essential function. Pharmacological inhibitor of farnesyl transferase activity also resulted in cytostasis of C. neoformans. Conclusion: Protein farnesylation is required for the growth of C. neoformans and may provide novel targets for antifungal therapy.
Full conference title:
The 15 th Congress of the International Society for Human and Animal Mycology
- ISHAM 15th (2003)