Comparative and functional genomics in the evolutionary study of emerging pathogens in the Sporothrix-sporotrichosis system.

Abstract

Sporotrichosis is a neglected and emerging disease among humans and animals. The disease is caused upon traumatic introduction of Sporothrix into the cutaneous and subcutaneous tissues of the host, with local lymphatic dissemination. Sporothrix often associated with mammals infection include S. brasiliensis, S. schenckii, S. globosa and S. luriei, which form a monophyletic clade called S. schenckii complex. Basal Sporothrix lineages are embedded in an environmental clade, and are phylogenetically flanked by Ophiostoma spp. related to soil, decaying wood and insects. Recent evidence demonstrated the emergence of pathogenicity in S. schenckii complex as a threat to the mammalian host. In this context, the main objective of this project is to understand how different Sporothrix, phylogenetically deviating, are able to infect humans and animals. The suggested approach involves the sequencing of entire genomes of a variety of pathogenic and non-pathogenic Sporothrix spp., in addition to comparative and functional analysis among agents with different ecologies within the Ophiostomatales. Comparative analyses of Sporothrix genomes will not only reveal great insights into the evolution of the Ophiostomatales (genome structure, global synteny, lineage-specific regions), but will allow us to identify groups of genes specifically linked to virulence factors and survival mechanisms during infection. Functional genomics analyses based on Sporothrix gene expression profiles will allow us to explore several virulence factors, important metabolic pathways, as well as several protein encoding genes and small RNAs not previously associated with infection in Sporothrix. The main expectation of this project is to increase significantly our understanding of the genetic diversity and physiological response in Sporothrix, a first step toward the development of better methods for pathogen control.