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eCAM Advance Access originally published online on August 18, 2004
eCAM 2004 1(2):167-174; doi:10.1093/ecam/neh033
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© 2004, the authors Evidenced-based Complementary and Alternative Medicine, Vol. 1, Issue 2 © Oxford University Press 2004; all rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated.

Original Article

Antiprotozoan and Antiviral Activities of Non-cytotoxic Truncated and Variant Analogues of Mussel Defensin

Philippe Roch1,*, Alain Beschin2 and Eric Bernard3

1Pathogènes et Immunité, UMR Ecosystèmes Lagunaires, Université de Montpellier 2 France, 2Department of Immunology, Parasitology and Ultrastructure, Flemish Interuniversity Institute for Biotechnology, Free University Brussels (VUB) Belgium, and 3Infectious Rétrovirales et Signalisation Cellulaire, UMR 5121, Institut de Biologie, Université de Montpellier 1 France

We previously reported the crucial role displayed by loop 3 of defensin isolated from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and antifungal activities. We now investigated antiprotozoan and antiviral activities of some previously reported fragments B, D, E, P and Q. Two fragments (D and P) efficiently killed Trypanosoma brucei (ID50 4–12 µM) and Leishmania major (ID50 12–45 µM) in a time/dose-dependent manner. Killing of T. brucei started as early as 1 h after initiation of contact with fragment D and reached 55% mortality after 6 h. Killing was temperature dependent and a temperature of 4°C efficiently impaired the ability to kill T. brucei. Fragments bound to the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was obtained only with fragments P and Q at 20 µM. Even if fragment P was active on both targets, the specificity of fragments D and Q suggest that antiprotozoan and antiviral activities are mediated by different mechanisms. Truncated sequences of mussel defensin, including amino acid replacement to maintain 3D structure and increased positive net charge, also possess antiprotozoan and antiviral capabilities. New alternative and/or complementary antibiotics can be derived from the vast reservoir of natural antimicrobial peptides (AMPs) contained in marine invertebrates.

Keywords: Trypanosoma – Leishmania – HIV – antibiotics – protozoa – virus – defensin – mussel

*For reprints and all correspondence: Philippe Roch, Université de Montpellier 2, cc 093, Place E. Bataillon, 34095 Montpellier cedex 5, France. E-mail: proch{at}univ-montp2.fr


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