Therapeutic activity of a killer peptide against experimental paracoccidioidomycosis

• Autor(a) principal: Travassos, Luiz R [UNIFESP]
• Data de Publicação: 2004
• Outros Autores: Silva, Luis. S. [UNIFESP], Rodrigues, Elaine G. [UNIFESP], Conti, S., Salati, A., Magliani, W., Polonelli, L.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1093/jac/dkh430; http://repositorio.unifesp.br/handle/11600/27990
• topic: anti-idiotypic fragments; killer mimotopes; paracoccidioidomycosis

Objectives: To evaluate whether an engineered synthetic decapeptide (KP) derived from the sequence of a recombinant anti-idiotypic antibody, that represents the internal image of a Pichia anomala killer toxin, could be fungicidal in vitro and therapeutic in vivo against Paracoccidioides brasiliensis and paracoccidioidomycosis (PCM).Methods: Fungicidal activity of KP was assessed in vitro and in vivo by inhibition of colony forming units and by histological examination, 8 days after infection, of organs from mice intravenously injected with a virulent strain of P. brasiliensis (3 x 10(6) yeast cells) and intraperitoneally treated with KP (3.3 mug/g body weight, three doses), in comparison with control animals equally administered with a scrambled decapeptide (SP).Results: KP but not SP was fungicidal in vitro at 39 ng/multiply-budding yeast cell and less efficiently in its D-isomeric form (0.31 mug/multiply-budding yeast cell). It was also able to markedly reduce the fungal load in organs (liver, lung, spleen) of infected animals.Conclusions: the therapeutic effect observed opens the way for using the antifungal peptide as an alternative control of PCM in association with conventional antifungal drugs.