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.
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 brasiliensis14-3-3 protein were selected based on its immunogenicity and therapeutic potential. METHODS: The in vitro antifungal activity and cytotoxicity of the 14-3-3peptides 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.
Authors: Chong W Ong; Sharon C-A Chen; Julia E Clark; Catriona L Halliday; Sarah E Kidd; Deborah J Marriott; Caroline L Marshall; Arthur J Morris; C Orla Morrissey; Rita Roy; Monica A Slavin; Andrew J Stewardson; Leon J Worth; Christopher H Heath Journal: Intern Med J Date: 2019-10 Impact factor: 2.048
Authors: Alexander Zaborin; Kathleen Romanowski; Svetlana Gerdes; Christopher Holbrook; Francois Lepine; Jason Long; Valeriy Poroyko; Stephen P Diggle; Andreas Wilke; Karima Righetti; Irina Morozova; Trissa Babrowski; Donald C Liu; Olga Zaborina; John C Alverdy Journal: Proc Natl Acad Sci U S A Date: 2009-04-06 Impact factor: 11.205
Authors: José F Muñoz; Rhys A Farrer; Christopher A Desjardins; Juan E Gallo; Sean Sykes; Sharadha Sakthikumar; Elizabeth Misas; Emily A Whiston; Eduardo Bagagli; Celia M A Soares; Marcus de M Teixeira; John W Taylor; Oliver K Clay; Juan G McEwen; Christina A Cuomo Journal: mSphere Date: 2016-09-28 Impact factor: 4.389
Authors: Leandro B R Silva; Lucas S Dias; Glauce M G Rittner; Julián E Muñoz; Ana C O Souza; Joshua D Nosanchuk; Luiz R Travassos; Carlos P Taborda Journal: Front Microbiol Date: 2017-06-14 Impact factor: 5.640
Authors: Adeline L Jorjão; Luciane D Oliveira; Liliana Scorzoni; Lívia Mara A Figueiredo-Godoi; Marcia Cristina A Prata; Antonio Olavo C Jorge; Juliana C Junqueira Journal: Virulence Date: 2018-01-01 Impact factor: 5.882
Authors: Scott Alper; Sandra J McBride; Brad Lackford; Jonathan H Freedman; David A Schwartz Journal: Mol Cell Biol Date: 2007-05-25 Impact factor: 4.272