A Metabolomic Investigation of the Effect of Eosin B on Game-tocyte of Plasmodium falciparum Using 1HNMR Spectroscopy
AbstractBackground: Recently eosin B was shown to have an effect on the asexual stage of Plasmodium falciparum and in this study, its activity against gametocytes and changes in the culture medium metabolites were investigated using an1HNMR-based metabolomics approach. Methods: In the Biochemistry Department of Pasteur Institute of Iran in 2017, parasites were cultured and gametocytogenesis induced by heparin and 5% hematocrit. Sexual stage parasites were tested by eosin B in 90 well plates and IC50 determined using Lactate Dehydrogenase assay. Gametocytes were treated by IC50 dose of eosin B and the medium collected in the two groups: with eosin B and controls and sent for 1HNMR spectroscopy. The spectra were analyzed on MATLAB interface and the altered metabolites in the culture medium and eosin-affected biochemical pathways were identified by Human Metabolome Database and Metaboanalyst website. Results: The results revealed eosin B had an effective gametocytocidal activity against P. falciparum. The significant metabolites changed in the medium were thiamine, Asp, Asn, Tyr, Lys, Ala, Phenylpyruvic acid, NAD+ and lipids. The main pathways identified were aminoacyl-tRNA biosynthesis, Phenylalanine, tyrosine and tryptophan biosynthesis, Alanine, aspartate and glutamate metabolism, Phenylalanine metabolism, Nicotinate and nicotinamide metabolism, and lysine degradation. Conclusion: Eosin B exhibited substantial gametocytocidal activity and affected important drug targets in the Plasmodium.
World Health Organization, World Malaria Report 2016, http://www.who.int/entity/malaria/publications/world-malaria-report-2016/report/en/index.html
Staines Henry M., and Sanjeev Krishna .Treatment and Prevention of Malaria. Springer Basel AG, 2012.
Roncalés María, Jaume Vidal-Mas, Didier Leroy, and Esperanza Herreros. "Comparison and optimization of different methods for the in vitro production of Plasmodium falciparum gametocytes. "Journal of parasitology research 2012 (2012) https://www.hindawi.com/journals/jpr/2012/927148/abs/
Massimine Kristen M., Michael T. McIntosh, Lanxuan T. Doan, Chloé E. Atreya, Stephan Gromer, Worachart Sirawaraporn, David A. Elliott, Keith A. Joiner, R. Heiner Schirmer, and Karen S. Anderson. "Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum." Antimicrobial agents and chemotherapy 50, no. 9 (2006) http://aac.asm.org/content/50/9/3132.full
Zamani Zahra, Alireza Sadeghi Tafreshi, Hossein Nahrevanian, Behzad Lame-Rad, Fatemeh Pourfallah, Hossein Eslamifar, Sedigheh Sadeghi, FaridehVahabi, Ayda Iravani, and Mohammad Arjmand."Efficacy of Eosin B as a New Antimalarial Drug in a Murine Model. "Malaria research and treatment 2012 (2012).https://www.hindawi.com/journals/mrt/2012/381724/
Sophie H. Adjalley, Geoffrey L. Johnston, Tao Li, Richard T. Eastman, Eric H. Ekland, Abraham G. Eappen, Adam Richman, B. Kim Lee Sim, Marcus C. S. Lee, Stephen L. Hoffman, and David A. Fidock "Quantitative assessment of Plasmodium falciparum sexual development reveals potent transmission-blocking activity by methylene blue." Proceedings of the National Academy of Sciences 108, no. 47 (2011): E1214-E1223.
Beckonert, Olaf, Hector C. Keun, Timothy MD Ebbels, Jacob Bundy, Elaine Holmes, John C. Lindon, and Jeremy K. Nicholson. "Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts." Nature protocols 2, no. 11 (2007): 2692-2703. https://www.ncbi.nlm.nih.gov/pubmed/18007604
Paget, Timothy, Nicolas Haroune, Sushmita Bagchi, and Edward Jarroll. "Metabolomics and protozoan parasites. "Actaparasitologica 58, no. 2 (2013): 127-131.
Lakshmanan, Viswanathan, Kyu Y. Rhee, and Johanna P. Daily. "Metabolomics and malaria biology. "Molecular and biochemical parasitology 175, no. 2 (2011): 104-111.
Trager, W. and Jensen, J.B., 1976. Human malaria parasites in continuous culture. Science, 193(4254),673-675.
Miao, J., Wang, Z., Liu, M., Parker, D., Li, X., Chen, X. and Cui, L., 2013.Plasmodium falciparum: generation of pure gametocyte culture by heparin treatment. Experimental parasitology, 135(3), 541-545. https://www.ncbi.nlm.nih.gov/pubmed/24055216
Moll, Kirsten, Akira Kaneko, Artur Scherf, and Mats Wahlgren. "Methods in Malaria Research." (2013) http://fliphtml5.com/dcfj/sotp/basic
Makler, Michael T., and David J. Hinrichs. "Measurement of the lactate dehydrogenase activity of Plasmodium falciparum as an assessment of parasitemia." The American journal of tropical medicine and hygiene 48, no. 2 (1993): 205-210.
Reader, Janette, Mariëtte Botha, AnjoTheron, Sonja B. Lauterbach, Claire Rossouw, DewaldtEngelbrecht, Melanie Wepener et al. "Nowhere to hide: interrogating different metabolic parameters of Plasmodium falciparum gametocytes in a transmission blocking drug discovery pipeline towards malaria elimination." Malaria journal 14, no. 1 (2015): 213. https://malariajournal.biomedcentral.com/articles/10.1186/s12936-015-0718-z
D'alessandro, Sarah, Francesco Silvestrini, Koen Dechering, Yolanda Corbett, Silvia Parapini, Martijn Timmerman, LauraGalastri et al. "A Plasmodium falciparum screening assay for anti-gametocyte drugs based on parasite lactate dehydrogenase detection." Journal of Antimicrobial Chemotherapy 68, no. 9 (2013): 2048-2058.
R. Viant, Improved Methods for the Acquisition and Interpretation of NMR Metabolomic Data, Biochem. Biophys. Res. Comm. 310, 943-948 (2003) https://www.ncbi.nlm.nih.gov/pubmed/14550295
Xia, J. and Wishart, D.S. 2016. Using MetaboAnalyst 3.0 for comprehensive metabolomics data analysis.Curr.Protoc.Bioinform. 55:14.10.1-14.10.91. doi: 10.1002/cpbi.11https://www.ncbi.nlm.nih.gov/pubmed/27603023
Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, et al., HMDB 3.0 — The Human Metabolome Database in 2013. Nucleic Acids Res. 2013. Jan 1;41(D1):D801-7. 23161693
Kanehisa, Minoru, and Susumu Goto. "KEGG: kyoto encyclopedia of genes and genomes." Nucleic acids research 28, no. 1 (2000): 27-30 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC102409/
Abdul-Ghani, Rashad, and John C. Beier. "Strategic use of antimalarial drugs that block falciparum malaria parasite transmission to mosquitoes to achieve local malaria elimination."Parasitology research 113, no. 10 (2014): 3535-3546. https://www.ncbi.nlm.nih.gov/pubmed/25185662
Eziefula, Alice C., Roly Gosling, Jimee Hwang, Michelle S. Hsiang, TeunBousema, Lorenz von Seidlein, and Chris Drakeley. "Rationale for short course primaquine in Africa to interrupt malaria transmission."Malaria journal 11, no. 1 (2012): 360. https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-11-360
Peatey, Christopher L., Tina S. Skinner-Adams, Matthew WA Dixon, James S. McCarthy, Donald L. Gardiner, and Katharine R. Trenholme. "Effect of antimalarial drugs on Plasmodium falciparum gametocytes." The Journal of infectious diseases 200, no. 10 (2009): 1518-1521. https://www.ncbi.nlm.nih.gov/pubmed/19848586
Peatey, Christopher L., Didier Leroy, Donald L. Gardiner, and Katharine R. Trenholme. "Anti-malarial drugs: how effective are they against Plasmodium falciparum gametocytes?." Malaria journal 11, no. 1 (2012): 34. https://www.ncbi.nlm.nih.gov/pubmed/22305482
Huthmacher, Carola, Andreas Hoppe, Sascha Bulik, and Hermann-Georg Holzhütter. "Antimalarial drug targets in Plasmodium falciparum predicted by stage-specific metabolic network analysis." BMC systems biology 4, no. 1 (2010): 120. https://www.ncbi.nlm.nih.gov/pubmed/20807400
Lamour, Sabrina D., Ursula Straschil, Jasmina Saric, and Michael J. Delves. "Changes in metabolic phenotypes of Plasmodium falciparum in vitro cultures during gametocyte development." Malaria journal 13, no. 1 (2014): 468. https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-13-468
Khan, Sameena. "Recent advances in the biology and drug targeting of malaria parasite aminoacyl-tRNAsynthetases." Malaria journal 15, no. 1 (2016): 203. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828885/
Pham, J.S., Dawson, K.L., Jackson, K.E., Lim, E.E., Pasaje, C.F.A., Turner, K.E. and Ralph, S.A., 2014.Aminoacyl-tRNAsynthetases as drug targets in eukaryotic parasites. International Journal for Parasitology: Drugs and Drug Resistance, 4(1), 1-13.
McConkey, G.A., 1999. Targeting the shikimate pathway in the malaria parasite Plasmodium falciparum. Antimicrobial agents and chemotherapy, 43(1), 175-177. https://www.ncbi.nlm.nih.gov/pubmed/9869588
Parvazi, Shirin, Sedigheh Sadeghi, MehriAzadi, Maryam Mohammadi, Mohammad Arjmand, Farideh Vahabi, Somye Sadeghzadeh, and Zahra Zamani. "The effect of aqueous extract of cinnamon on the metabolome of Plasmodium falciparum using 1HNMR spectroscopy."Journal of tropical medicine 2016 (2016).
Forth, Thomas. "Metabolic systems biology of the malaria parasite." PhD thesis., University of Leeds, 2012. http://etheses.whiterose.ac.uk/3739/
Sharma, Arvind, and Amit Sharma. "Plasmodium falciparum mitochondria import tRNAs along with an active phenylalanyl-tRNAsynthetase." Biochemical Journal 465, no. 3 (2015): 459-469.
O'Hara, Jessica K., Lewis J. Kerwin, Simon A. Cobbold, Jonathan Tai, Thomas A. Bedell, Paul J. Reider, and Manuel Llinás. "Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum."PLoS One 9, no. 4 (2014): e94061. https://www.ncbi.nlm.nih.gov/pubmed/24747974
Chua, Hwa Huat, High-content screening of antimalarial drugs using metabolomic approaches, 2016, PhD thesis, https://minerva-access.unimelb.edu.au/handle/11343/128079
Trenholme, Katharine, Linda Marek, Sandra Duffy, Gabriele Pradel, Gillian Fisher, Finn K. Hansen, Tina S. Skinner-Adams et al. "Lysine acetylation in sexual stage malaria parasites is a target for antimalarial small molecules." Antimicrobial agents and chemotherapy 58, no. 7 (2014): 3666-3678. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068603/
Bouyou-Akotet, M. K., D. P. Mawili Mboumba, V. Guiyedi, M. Pemba Mihindou, and M. Maryvonne Kombila."Altered total cholesterol and triglyceride levels during the course of Plasmodium falciparum infection in children."Journal of Parasitology and Vector Biology 6, no. 11 (2014): 174-180. http://www.academicjournals.org/journal/JPVB/article-abstract/5114D8C49032
Debierre-Grockiego, Françoise, Louis Schofield, Nahid Azzouz, Jörg Schmidt, Cristiana Santos de Macedo, Michael AJ Ferguson, and Ralph T. Schwarz. "Fatty acids from Plasmodium falciparum down-regulate the toxic activity of malaria glycosylphosphatidylinositols." Infection and immunity 74, no. 10 (2006): 5487-5496.
Visser, Benjamin J., Rosanne W. Wieten, Ingeborg M. Nagel, and Martin P. Grobusch."Serum lipids and lipoproteins in malaria-a systematic review and meta-analysis." Malaria journal 12, no. 1 (2013): 442. https://malariajournal.biomedcentral.com/articles/10.1186/1475-2875-12-442