Resumo

Paracoccidioides spp is the causal agent of paracoccidioidomycosis (PCM), one of the most important deep systemic and endemic mycosis in Latin America. The natural infection is assumed to be the inhalation of airborne propagules produced by the fungal mycelium form, which then change into the pathogenic yeast form in the lung, subsequently can disseminate to the other organs. There are distinct forms of PCM, and treatment regimens of longer duration are required to treat patients with the more severe forms that resulting in intoxicating and even in therapy relapse. In addition, cases of PCM associated with AIDS have been recently reported. The glyoxylate cycle and its key enzymes isocitrate lyase and malate synthase play a crucial role in the pathogenicity and virulence of various fungi such as the human pathogens. Here we showed that isocitrate lyase of Paracoccidioides (PbICL) is localized at cell wall and cytoplasm. PbICL and the respective polyclonal antibody inhibited the interaction of Paracoccidioides spp to A549 cells. The recombinant PbICL binds to fibronectin and type IV collagen. These results suggest that PbICL is required for interactions between Paracoccidioides spp and extracellular matrix components, and that this interaction may play an important role in the fungal adherence and invasion to host cells. Argentilactone, the major constituent of essential oil of Hyptis ovalifolia, is an abundant natural product from Brazilian Savannah flora and has structural similarity with isocitrate, the substrate to isocitrate lyase. So we also investigated if argentilactone inhibit the adhesion of the protein to extracellular matrix components fibronectin and collagen IV by using ELISA, Far-Western blot assays and fluorescence microscopy by IN CELL. The results showed that argentilactone interfered in the adhesion de Paracoccidioides spp yeast cells and PbICL to fibronectin and collagen IV of cell lines A549 and MRC5.