JAC Advance Access originally published online on September 24, 2004
Journal of Antimicrobial Chemotherapy 2004 54(5):956-958; doi:10.1093/jac/dkh430
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JAC vol.54 no.5 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved
Therapeutic activity of a killer peptide against experimental paracoccidioidomycosis
1 Universidade Federal de São Paulo, Unidade de Oncologia Experimental, Departamento de Microbiologia, Imunologia e Parasitologia, 04023–062 São Paulo, Brazil; 2 Dipartimento di Patologia e Medicina di Laboratorio, Sezione di Microbiologia, Università degli Studi di Parma, Viale Gramsci 14, 43100 Parma, Italy
* Corresponding author. Tel: +39-521-988885; Fax: +39-521-993620; Email: lucpol{at}unipr.it
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 µg/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 µg/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.
Keywords: anti-idiotypic fragments , killer mimotopes , paracoccidioidomycosis
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