Email updates

Keep up to date with the latest news and content from BMC Proceedings and BioMed Central.

This article is part of the supplement: Institut Pasteur International Network Annual Scientific Meeting

Open Access Lecture presentation

Networking the Leishmania research community for the development of novel anti-leishmanial intervention strategies

Gerald F Späth

  • Correspondence: Gerald F Späth

Author Affiliations

G5 Virulence Parasitaire, Institut Pasteur, CNRS URA 2581, INSERM U1010, 75015 Paris, France

BMC Proceedings 2011, 5(Suppl 1):L8  doi:10.1186/1753-6561-5-S1-L8

The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1753-6561/5/S1/L8


Published:10 January 2011

© 2011 Späth; licensee BioMed Central Ltd.

This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Lecture presentation

The EU-sponsored LEISHDRUG consortium uses a highly interdisciplinary approach to reveal Leishmania signaling molecules associated with virulence of the pathogenic amastigote stage. LEISHDRUG coordinates the efforts of 13 partners across eight nations, including four institutes of the Institut Pasteur international network, with the major aim to exploit the Leishmania kinome for anti-parasitic drug development.

The consortium is based on three clusters with each two interactive scientific work packages that together follow the major stages of the drug development process, including identification of hit compounds and target kinases, hit-to-lead validation and lead characterization. We use innovative drug screening concepts not applied previously on parasitic systems, including visual high-content screening to discover compounds capable to kill intracellular Leishmania amastigotes without deteriorating the host cell. This phenotype-based strategy relies on fluorescent parasites and macrophages as read-outs and will allow simultaneous assessment of anti-leishmanial activity and host cell toxicity under physiological conditions. We apply a target-based strategy utilizing recombinant Leishmania protein kinases for inhibitor identification and structure-guided drug design. The identification of appropriate target kinases, with only limited homology to their mammalian counterparts relies on in silico analysis by applying novel bioinformatic tools developed by consortium members, and in vitro assays based on their phospho-transferase activity towards recombinant Leishmania phospho-proteins.

The major objectives of our consortium are (i) to screen small molecule and peptide libraries for hit compounds with leishmanicidal activity using phenotype- and target-based strategies, (ii) to identify anti-parasitic lead compounds and assess their pharmacokinetic profiles using cell-culture and experimental infection models for leishmaniasis, and (iii) to initiate lead optimization by structure-based drug design.