High content live cell imaging for the discovery of new antimalarial marine natural products

BMC Infectious Diseases

Research Article

Matthew Bruton¹  Karine G Le Roch¹  Michael Cervantes¹  Jacques Prudhomme¹  Serena Cervantes¹  David Carter²  William Aalbersberg³  Young Tae-Chang⁴  Mark E Hay⁵  Sebastian Engel⁶  Julia Kubanek⁷  Paige E Stout⁷ 

[1] Department of Cell Biology and Neuroscience, University of California Riverside, 92521, Riverside, CA, USA;Institute for Integrative Genome Biology, University of California, 92521, Riverside, CA, USA;Institute of Applied Sciences, University of the South Pacific, Suva, Fiji;Laboratory of Bioimaging Probe Development, Singapore Bioimaging Consortium, 138667, Biopolis, Singapore;Agency for Science, Technology and Research (A*STAR), 138667, Biopolis, Singapore;School of Biology, Georgia Institute of Technology, 30332, Atlanta, GA, USA;School of Chemistry and Biochemistry, Georgia Institute of Technology, 30332, Atlanta, GA, USA;School of Chemistry and Biochemistry, Georgia Institute of Technology, 30332, Atlanta, GA, USA;School of Biology, Georgia Institute of Technology, 30332, Atlanta, GA, USA;

关键词: Plasmodium falciparum;    Drug screening;    Natural products;    Antimalarial;    High-throughput screening;   

DOI  :  10.1186/1471-2334-12-1

 received in 2011-06-22, accepted in 2012-01-03,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThe human malaria parasite remains a burden in developing nations. It is responsible for up to one million deaths a year, a number that could rise due to increasing multi-drug resistance to all antimalarial drugs currently available. Therefore, there is an urgent need for the discovery of new drug therapies. Recently, our laboratory developed a simple one-step fluorescence-based live cell-imaging assay to integrate the complex biology of the human malaria parasite into drug discovery. Here we used our newly developed live cell-imaging platform to discover novel marine natural products and their cellular phenotypic effects against the most lethal malaria parasite, Plasmodium falciparum.MethodsA high content live cell imaging platform was used to screen marine extracts effects on malaria. Parasites were grown in vitro in the presence of extracts, stained with RNA sensitive dye, and imaged at timed intervals with the BD Pathway HT automated confocal microscope.ResultsImage analysis validated our new methodology at a larger scale level and revealed potential antimalarial activity of selected extracts with a minimal cytotoxic effect on host red blood cells. To further validate our assay, we investigated parasite's phenotypes when incubated with the purified bioactive natural product bromophycolide A. We show that bromophycolide A has a strong and specific morphological effect on parasites, similar to the ones observed from the initial extracts.ConclusionCollectively, our results show that high-content live cell-imaging (HCLCI) can be used to screen chemical libraries and identify parasite specific inhibitors with limited host cytotoxic effects. All together we provide new leads for the discovery of novel antimalarials.

【 授权许可】

Unknown   
© Cervantes et al; licensee BioMed Central Ltd. 2011. This article is published under license to 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.