| Autor: |
Marcos CM; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil., de Oliveira HC; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil.; Instituto Carlos Chagas, Fundação Oswaldo Cruz (Fiocruz), Curitiba 81350-010, Brazil., Assato PA; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil.; Laboratório Central de Multiusuários, Faculdade de Ciências Agronômicas, Campus Botucatu, UNESP-Universidade Estadual Paulista, São Paulo 18610-034, Brazil., de Oliveira LT; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil., Fregonezi N; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil., Dos Santos KS; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil., Costa-Orlandi CB; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil., Fusco-Almeida AM; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil., Mendes-Giannini MJS; School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil. |
| Abstrakt: |
Considering the toxicity of conventional therapeutic approaches and the importance of precise mechanistic targets, it is important to explore signaling pathways implicated in fungal pathobiology. Moreover, treatment of paracoccidioidomycosis, a systemic mycosis caused by a dimorphic fungus, requires prolonged therapeutic regimens. Among the numerous factors underpinning the establishment of Paracoccidioides spp. infection, the capacity to transition from the mycelial to the yeast form is of pivotal importance. The Drk1 protein of Paracoccidioides brasiliensis likely plays a decisive role in this morphological shift and subsequent virulence. We identified peptides with affinity for the PbDrk1 protein using the phage-display method and assessed the effects of these peptides on P. brasiliensis . The peptides were found to inhibit the phase transition of P. brasiliensis. Furthermore, a substantial proportion of these peptides prevented adhesion to pneumocytes. Although these peptides may not possess inherent antifungal properties, they can augment the effects of certain antifungal agents. Notably, the cell wall architecture of P. brasiliensis appears to be modulated by peptide intervention, resulting in a reduced abundance of glycosylated proteins and lipids. These peptides were also evaluated for their efficacy in a Galleria mellonella model and shown to contribute to enhanced larval survival rates. The role of PbDrk1, which is notably absent in mammals, should be further investigated to improve the understanding of its functional role in P. brasiliensis , which may be helpful for designing novel therapeutic modalities. |
