Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis

Abstract

The fungi of the Paracoccidioides genus are dimorphic fungi, etiological agents of paracoccidioidomycosis (PCM), systemic mycosis of great interest in Latin America and Brazil. The antifungal arsenal available for PCM treatment is limited and most agents have high toxicity. The search for new agents that innovate the mechanism of action are of outmost importance and urgency for the treatment of PCM as well as for the treatment of other systemic mycoses. In innovative terms, difficult the adhesion of the fungus to host cells can be an efficient way in helping to combat the infection, once unable to adhere, the fungus will be unable to colonize different host tissues, the nutrients acquiring will be difficult, facilitating the host immune system to combat the infection. In this sense, the candidate for post-doctoral scholarship during his PhD study, due to the importance of the adhesion in the infection process of Paracoccidioides spp., using Phage Display, was able to identify four peptides that bind with high affinity to Paracoccidioides spp. cell wall, with ability to inhibit adhesion of the fungus to the host structures in vitro, reduce the virulence of the fungus and, in addition, modulate the host immune system generating a more effective response in resolving the infection and these results show the importance of invest in the characterization of these peptides for use in the treatment and prophylaxis of PCM. Because of these characteristics, this project aims to use murine model to establish which kind of response that immunizations with these peptides can cause to the host, what course will the infection take in mice treated with the peptides and what the effects of immunization with the peptides followed by the known treatment of the disease. The project also aims to better characterize these peptides, defining the targets to which they bind in the fungus cell wall as well as increasing the scope of use of these peptides in other fungal species of medical importance as Histoplasma capsulatum, Cryptococcus neoformans and Candida albicans evaluating aspects such as influence on virulence and biofilm formation.