Anotação funcional e genômica comparativa de vias metabólicas de Cryptococcus spp.

Abstract

Cryptococcus neoformans and C. gattii are the main agents of Cryptococcosis, a systemic mycosis that affects lungs, tending to migrate to the Central Nervous System. These species share almost all the virulence factors. However, different patterns of hosts are observed for these microorganisms. One hypothesis for this is that differences in the metabolism of these pathogens could occur. Bioinformatics represents an area of studies that allows the analysis of in silico data provided from genomic sequencing and other Molecular Biology techniques. The use of computational tools allows the study of structures like DNA, RNA and proteins, as well as the prediction of metabolic pathways of organisms and the comparison of them with other pathways. Therefore, the aim of this study was to characterize, in silico, metabolic pathways of C. neoformans and C. gattii, as well as their functions, besides to identify the presence of sequences that code virulence factors of these organisms, by analyzing genome sequences available in public databases. Three genomes of C. neoformans and three of C. gattii with genomic and functional annotation were used. In order to contribute to the functional annotation of these genomes, it was performed the prediction of ribosomal RNAs and transfer RNAs for each strain used. A sequence similarity search between strains within the same species was performed, and it was observed a high level of sequence conservation in the level of nucleotides. The predicted proteomes were extracted from the genomes and the metabolic pathways mapping was performed by Blast2GO. From the 29 metabolic pathways mapped, 16 were common to all organisms. The results obtained from the cluster analysis demonstrated that almost all of the proteins associated with virulence belong to the core genome. It was also observed that proteins associated with virulence are involved in several biological processes. Moreover, it was evidenced that the strain C. neoformans H99 was the only one to pursue enzymes associated with virulence mapped in the oxidative phosphorylation pathway, being this a possible target for future studies. Based on the results obtained in this study, we concluded that studies about metabolic pathways of Cryptococcus spp. are extremely important for a better understanding about the mechanisms involved in the virulence of these pathogens.