This research proposal is for a molecular genetic study of the self- splicing group I intron of Pneumocystis carinii, which is being characterized as a potential new RNA target for the development of antimicrobial chemotherapeutics agents. An in vivo surrogate organism system in which this intron is transfered to yeast nuclear genes is proposed to perform antibiotic sensitivity assays using pentamidine and others in vitro P. carinii group I ribosome splicing inhibitors. The structure-function relationship analysis of antibiotic resistance mutants will be used to propose new splicing inhibitors in vivo. Due to the absence of culture systems for this opportunistic pathogen and the need for more effective alternative drugs, this novel system represents a fast and inexpensive way to screen chemicals in vivo, as well as a model system to facilitate the development of new drugs acting on group I introns.
| Miletti-Gonzalez, Karl E; Leibowitz, Michael J (2008) Molecular characterization of two types of rDNA units in a single strain of Candida albicans. J Eukaryot Microbiol 55:522-9 |
