IMR Press / FBE / Volume 10 / Issue 2 / DOI: 10.2741/E820

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article

Development of a semi-automated image-based high-throughput drug screening system

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1 Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland
2 Access Platform Swiss National Centre of Competence in Research (NCCR), University of Geneva, 1211 Geneva, Switzerland
3 Biomolecular Screening Facility, Ecole Polytechnique Federale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland
4 Department of Molecular Microbiology, School of Medicine, Washington University, St. Louis, MO 63110, USA

*Author to whom correspondence should be addressed.

Front. Biosci. (Elite Ed) 2018, 10(2), 242–253; https://doi.org/10.2741/E820
Published: 1 January 2018
Abstract

We previously reported that the innate sensing of the endosymbiont Leishmania RNA virus 1 (LRV1) within Leishmania (Viannia) guyanensis through Toll-like receptor 3, worsens the pathogenesis of parasite infection in mice. The presence of LRV1 has been associated with the failure of first-line treatment in patients infected with LRV1 containing -L. guyanensis and -L. braziliensis parasites. Here, we established a semi-automated image-based high-throughput drug screening (HTDS) protocol to measure parasiticidal activity of the Prestwick chemical library in primary murine macrophages infected with LRV1-containing L. guyanensis. The two-independent screens generated 14 hit compounds with over sixty-nine percent reduction in parasite growth compared to control, at a single dose in both screens. Our screening strategy offers great potential in the search for new drugs and accelerates the discovery rate in the field of drug repurposing against Leishmania. Moreover, this technique allows the concomitant assessment of the effect of drug toxicity on host cell number.

Keywords
Leishmania
High-Content Microscope
Drug Screening
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