Multi-omics based identification of specific biochemical changes associated with PfKelch13-mutant artemisinin resistant Plasmodium falciparum.

作者: Ghizal Siddiqui , Anubhav Srivastava , Adrian S. Russell , Darren J. Creek

DOI: 10.1093/INFDIS/JIX156

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摘要: Background The emergence of artemisinin resistance in the malaria parasite Plasmodium falciparum poses a major threat to control and elimination malaria. Certain point mutations propeller domain PfKelch13 are associated with resistance, but do not always result clinical resistance. underlying mechanisms poorly understood, impact on cellular biochemistry is defined. Methods This study aimed identify global biochemical differences between PfKelch13-mutant artemisinin-resistant -sensitive strains P. by combining liquid chromatography-mass spectrometry (LC-MS)-based proteomics, peptidomics, metabolomics. Results Proteomics analysis found both examined be specifically decreased abundance protein. Metabolomics demonstrated accumulation glutathione its precursor, gamma-glutamylcysteine, significant depletion 1 other putative metabolite resistant strains. Peptidomics revealed lower several endogenous peptides derived from hemoglobin (HBα HBβ) Conclusion lead protein, digestion, enhanced production.

参考文章(49)
Rick M. Fairhurst, Understanding artemisinin-resistant malaria Current Opinion in Infectious Diseases. ,vol. 28, pp. 417- 425 ,(2015) , 10.1097/QCO.0000000000000199
William Trager, Cultivation of malaria parasites. Methods in Cell Biology. ,vol. 45, pp. 7- 26 ,(1995) , 10.1016/S0091-679X(08)61844-0
Jianguo Xia, Igor V. Sinelnikov, Beomsoo Han, David S. Wishart, MetaboAnalyst 3.0—making metabolomics more meaningful Nucleic Acids Research. ,vol. 43, ,(2015) , 10.1093/NAR/GKV380
Kellen L. Olszewski, Joanne M. Morrisey, Daniel Wilinski, James M. Burns, Akhil B. Vaidya, Joshua D. Rabinowitz, Manuel Llinás, Host-parasite interactions revealed by Plasmodium falciparum metabolomics. Cell Host & Microbe. ,vol. 5, pp. 191- 199 ,(2009) , 10.1016/J.CHOM.2009.01.004
Paul J Boersema, Reinout Raijmakers, Simone Lemeer, Shabaz Mohammed, Albert J R Heck, Multiplex peptide stable isotope dimethyl labeling for quantitative proteomics. Nature Protocols. ,vol. 4, pp. 484- 494 ,(2009) , 10.1038/NPROT.2009.21
J. Straimer, N. F. Gnadig, B. Witkowski, C. Amaratunga, V. Duru, A. P. Ramadani, M. Dacheux, N. Khim, L. Zhang, S. Lam, P. D. Gregory, F. D. Urnov, O. Mercereau-Puijalon, F. Benoit-Vical, R. M. Fairhurst, D. Menard, D. A. Fidock, K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates Science. ,vol. 347, pp. 428- 431 ,(2015) , 10.1126/SCIENCE.1260867
Linda Y Liu, Ting Yang, Jun Ji, Qiaojun Wen, Alexander A Morgan, Bo Jin, Gongxing Chen, Deirdre J Lyell, David K Stevenson, Xuefeng B Ling, Atul J Butte, Integrating multiple ‘omics’ analyses identifies serological protein biomarkers for preeclampsia BMC Medicine. ,vol. 11, pp. 236- 236 ,(2013) , 10.1186/1741-7015-11-236
Juri Rappsilber, Yasushi Ishihama, Matthias Mann, None, Stop and Go extraction tips for matrix-assisted laser desorption/ionization, nanoelectrospray, and lc/ms sample pretreatment in proteomics Analytical Chemistry. ,vol. 75, pp. 663- 670 ,(2003) , 10.1021/AC026117I
Bidii S. Ngalah, Luiser A. Ingasia, Agnes C. Cheruiyot, Lorna J. Chebon, Dennis W. Juma, Peninah Muiruri, Irene Onyango, Jack Ogony, Redemptah A. Yeda, Jelagat Cheruiyot, Emmanuel Mbuba, Grace Mwangoka, Angela O. Achieng, Zipporah Ng'ang'a, Ben Andagalu, Hoseah M. Akala, Edwin Kamau, Analysis of major genome loci underlying artemisinin resistance and pfmdr1 copy number in pre- and post-ACTs in western Kenya. Scientific Reports. ,vol. 5, pp. 8308- 8308 ,(2015) , 10.1038/SREP08308
R. Luise Krauth-Siegel, Joachim G. Muller, Friedrich Lottspeich, R. Heiner Schirmer, Glutathione Reductase and Glutamate Dehydrogenase of Plasmodium Falciparum, The Causative Agent of Tropical Malaria FEBS Journal. ,vol. 235, pp. 345- 350 ,(1996) , 10.1111/J.1432-1033.1996.00345.X