Therapeutic activity of a killer peptide against experimental 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 106 yeast cells) and intraperitoneally treated with KP (3.3 micrograms/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 (0.31micrograms/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.