Overexpression of paracoccin: phenotype and virulence of Paracoccidioides brasiliensis strains

Abstract

Paracoccidioides spp. fungi are pathogenic, thermally dimorphic and ethiologic agents of Paracoccidioidomycosis (PCM), the major mycosis in Latin America. The infected individual with Paracoccidioides spp. develops a response against the fungus as a way to eliminate it from by organism. The resistance to P. brasiliensis infection is associated with secretion of high levels of TNF-± and IFN-³. There are several efforts to characterize important components to fungal virulence by using gene knockdown techniques in different pathogenic fungi. Our group identified the paracoccin lectin in P. brasiliensis yeasts, which is the target of this project. This lectin binds to N-acetylglucosamine, contributes to the fungus growth and its adhesion to the extracellular matrix. Furthermore, the paracoccin induces macrophages to produce TNF-± and high concentrations of NO and interacts with TLR2 and TLR4. Considering the relevance of the biological roles of paracoccin, we propose to develop a molecular tool that increases its expression in P. brasiliensis, enabling the effects of overexpression of paracoccin in fungus and in the immune response in the host. The results that will be obtained should contribute to the understanding of the paracoccin role in fungus biology and in the experimental PCM. (AU)