K-057. A Genome Based Metabolic Model for the Fungal Pathogen Cryptococcus neoformans

S. Gonyea1, A. J. Reese1, S. Fong2;
1Cedar Crest Coll., Allentown, PA, 2Virginia Commonwealth Univ., Richmond, VA.

Cryptococcus neoformans is a pervasive soil-associated fungal threat to individuals who are immunocompromised. In the central nervous system, cryptococcal disease can present as severe meningitis-like symptoms. The pathogenicity of C. neoformans is largely due to the complex polysaccharide capsule that allows the cell to evade the body’s immune response. Much remains unclear about the interactions between the cell, the capsule, and the immune response. C. neoformans does not respond well to anti-fungals currently available and there is a need for the identification of new drug targets. The approach of this research is to systematically study the metabolism of C. neoformans based upon genomic and literature information. Specifically, a computational genome-based metabolic model is being constructed that will allow researchers to comprehensively study C. neoformans metabolism and to perform in silico simulations to predict gene and pathway usage in relation to phenotype in both wild-type and genetically-modified strains. Results from simulations can then be tested experimentally to validate the model’s accuracy. Errors in the model may lead to further clues about unusual or unannotated metabolic pathways present in C. neoformans. Similar models have been successfully constructed and used by other researchers to study organisms ranging from Escherichia coli to Homo sapiens. To date, 570 metabolic reactions have been determined for the C. neoformans model using sequence homology comparisons with Saccharomyces cerevisiae and literature evidence. These reactions are being analyzed with a new modeling software program, MetModel, to evaluate the coherence of the reconstructed network. Pathway similarities and differences between C. neoformans and S. cerevisiae will be presented. We are interested specifically in the capsular synthesis and assembly pathways unique to C. neoformans. This in silico metabolic model represents a novel approach to systematically studying proteins involved in these processes and may aid in the development of a way in which to prevent capsule attachment and establishment of infection by this fungal pathogen.