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JAC Advance Access published online on September 24, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh430
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received June 4, 2004
Revised August 12, 2004
Accepted August 16, 2004

Brief report

Therapeutic activity of a killer peptide against experimental paracoccidioidomycosis

Luiz R. Travassos 1, Luis S. Silva 1, Elaine G. Rodrigues 1, Stefania Conti 2, Antonella Salati 2, Walter Magliani 2, and Luciano Polonelli 2*

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

* To whom correspondence should be addressed. E-mail: lucpol{at}unipr.it.


  Abstract

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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