Abstract
Background: Paracoccidioidomycosis (PCM) is a chronic disease that causes sequelae and requires prolonged treatment; therefore, new therapeutic approaches are necessary. In view of this, three peptides from Paracoccidioides brasiliensis 14-3-3 protein were selected based on its immunogenicity and therapeutic potential. Methods: The in vitro antifungal activity and cytotoxicity of the 14-3-3 peptides were evaluated. The influence of the peptides in immunological and survival aspects was evaluated in vivo, using Galleria mellonella and the expression of antimicrobial peptide genes in Caenorhabditis elegans. Results: None of the peptides were toxic to HaCaT (skin keratinocyte), MRC-5 (lung fibroblast), and A549 (pneumocyte) cell lines, and only P1 exhibited antifungal activity against Paracoccidioides spp. The peptides could induce an immune response in G. mellonella. Moreover, the peptides caused a delay in the death of Paracoccidioides spp. infected larvae. Regarding C. elegans, the three peptides were able to increase the expression of the antimicrobial peptides. These peptides had essential effects on different aspects of Paracoccidioides spp. infection showing potential for a therapeutic vaccine. Future studies using mammalian methods are necessary to validate our findings.
Highlights
1.2 million people are affected by fungal infections; it is difficult to estimate the real incidence of fungal infections since there is no obligatory reporting of these diseases in many countries [1,2]
peptide 2 (P2) and peptide 3 (P3) induce the production of phenoloxidase with a 7.0 and 6.3-fold increase (p < 0.05), respectively when compared to larvae treated with phosphate-buffered saline (PBS) (Figure 5A)
The most significant increase in peptide expression occurred with the treatment of peptide 1 (P1) and P3, respectively, a 15-fold increase for galerimicin and a 6.8-fold increase in galiomycin expression compared to the untreated control
Summary
1.2 million people are affected by fungal infections; it is difficult to estimate the real incidence of fungal infections since there is no obligatory reporting of these diseases in many countries [1,2]. The infection occurs by inhalation of fungus propagules and affects, in most cases, children/young adults (acute form) or adult men (chronic condition) [6]. This infection has important medical, social, and economic impact since it affects people during the productive life period and can cause sequelae [8]. Regarding C. elegans, the three peptides were able to increase the expression of the antimicrobial peptides These peptides had essential effects on different aspects of Paracoccidioides spp. infection showing potential for a therapeutic vaccine. Future studies using mammalian methods are necessary to validate our findings
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