{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:12:44Z","timestamp":1790759564969,"version":"4.1.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T00:00:00Z","timestamp":1534896000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,8,22]],"date-time":"2018-08-22T00:00:00Z","timestamp":1534896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Artemisinin is the most rapidly effective drug for <jats:italic>Plasmodium falciparum<\/jats:italic> malaria treatment currently in clinical use. Emerging artemisinin-resistant parasites pose a great global health risk. At present, the level of artemisinin resistance is still relatively low with evidence pointing towards a trade-off between artemisinin resistance and fitness loss. Here we show that artemisinin-resistant <jats:italic>P. falciparum<\/jats:italic> isolates from Cambodia manifested fitness loss, showing fewer progenies during the intra-erythrocytic developmental cycle. The loss in fitness was exacerbated under the condition of low exogenous amino acid supply. The resistant parasites failed to undergo maturation, whereas their drug-sensitive counterparts were able to complete the erythrocytic cycle under conditions of amino acid deprivation. The artemisinin-resistant phenotype was not stable, and loss of the phenotype was associated with changes in the expression of a putative target, Exp1, a membrane glutathione transferase. Analysis of SNPs in haemoglobin processing genes revealed associations with parasite clearance times, suggesting changes in haemoglobin catabolism may contribute to artemisinin resistance. These findings on fitness and protein homeostasis could provide clues on how to contain emerging artemisinin-resistant parasites.<\/jats:p>","DOI":"10.1038\/s41598-018-30593-5","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T14:56:33Z","timestamp":1534431393000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Fitness Loss under Amino Acid Starvation in Artemisinin-Resistant Plasmodium falciparum Isolates from Cambodia"],"prefix":"10.1038","volume":"8","author":[{"given":"Duangkamon","family":"Bunditvorapoom","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theerarat","family":"Kochakarn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namfon","family":"Kotanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0739-006X","authenticated-orcid":false,"given":"Charin","family":"Modchang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krittikorn","family":"K\u00fcmpornsin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duangkamon","family":"Loesbanluechai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanyaluk","family":"Krasae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8338-1974","authenticated-orcid":false,"given":"Liwang","family":"Cui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kesinee","family":"Chotivanich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prapon","family":"Wilairat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8060-6771","authenticated-orcid":false,"given":"Olivo","family":"Miotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2876-6203","authenticated-orcid":false,"given":"Thanat","family":"Chookajorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,8,22]]},"reference":[{"key":"30593_CR1","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1126\/science.1155165","volume":"320","author":"NJ White","year":"2008","unstructured":"White, N. J. Qinghaosu (artemisinin): the price of success. Science 320, 330\u2013334 (2008).","journal-title":"Science"},{"key":"30593_CR2","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1038\/nrmicro2331","volume":"8","author":"AM Dondorp","year":"2010","unstructured":"Dondorp, A. M. et al. Artemisinin resistance: current status and scenarios for containment. Nat Rev Microbiol 8, 272\u2013280, https:\/\/doi.org\/10.1038\/nrmicro2331 (2010).","journal-title":"Nat Rev Microbiol"},{"key":"30593_CR3","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1056\/NEJMoa0808859","volume":"361","author":"AM Dondorp","year":"2009","unstructured":"Dondorp, A. M. et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 361, 455\u2013467 (2009).","journal-title":"N Engl J Med"},{"key":"30593_CR4","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1056\/NEJMoa1314981","volume":"371","author":"EA Ashley","year":"2014","unstructured":"Ashley, E. A. et al. Spread of artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med 371, 411\u2013423, https:\/\/doi.org\/10.1056\/NEJMoa1314981 (2014).","journal-title":"N Engl J Med"},{"key":"30593_CR5","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1086\/322858","volume":"184","author":"TE Wellems","year":"2001","unstructured":"Wellems, T. E. & Plowe, C. V. Chloroquine-resistant malaria. J Infect Dis 184, 770\u2013776, https:\/\/doi.org\/10.1086\/322858 (2001).","journal-title":"J Infect Dis"},{"key":"30593_CR6","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.pt.2013.08.002","volume":"29","author":"I Naidoo","year":"2013","unstructured":"Naidoo, I. & Roper, C. Mapping \u2018partially resistant\u2019, \u2018fully resistant\u2019, and \u2018super resistant\u2019 malaria. Trends Parasitol 29, 505\u2013515, https:\/\/doi.org\/10.1016\/j.pt.2013.08.002 (2013).","journal-title":"Trends Parasitol"},{"key":"30593_CR7","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1080\/14656566.2016.1187134","volume":"17","author":"NJ White","year":"2016","unstructured":"White, N. J. Can new treatment developments combat resistance in malaria? Expert Opin Pharmacother 17, 1303\u20131307, https:\/\/doi.org\/10.1080\/14656566.2016.1187134 (2016).","journal-title":"Expert Opin Pharmacother"},{"key":"30593_CR8","doi-asserted-by":"publisher","first-page":"5157","DOI":"10.1073\/pnas.1217452110","volume":"110","author":"N Klonis","year":"2013","unstructured":"Klonis, N. et al. Altered temporal response of malaria parasites determines differential sensitivity to artemisinin. Proc Natl Acad Sci USA 110, 5157\u20135162, https:\/\/doi.org\/10.1073\/pnas.1217452110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"30593_CR9","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/S1473-3099(13)70252-4","volume":"13","author":"B Witkowski","year":"2013","unstructured":"Witkowski, B. et al. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis 13, 1043\u20131049, https:\/\/doi.org\/10.1016\/S1473-3099(13)70252-4 (2013).","journal-title":"Lancet Infect Dis"},{"key":"30593_CR10","doi-asserted-by":"publisher","first-page":"3157","DOI":"10.1128\/AAC.01924-13","volume":"58","author":"K Chotivanich","year":"2014","unstructured":"Chotivanich, K. et al. Laboratory detection of artemisinin-resistant Plasmodium falciparum. Antimicrob Agents Chemother 58, 3157\u20133161, https:\/\/doi.org\/10.1128\/AAC.01924-13 (2014).","journal-title":"Antimicrob Agents Chemother"},{"key":"30593_CR11","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1126\/science.1215966","volume":"336","author":"IH Cheeseman","year":"2012","unstructured":"Cheeseman, I. H. et al. A major genome region underlying artemisinin resistance in malaria. Science 336, 79\u201382, https:\/\/doi.org\/10.1126\/science.1215966 (2012).","journal-title":"Science"},{"key":"30593_CR12","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1073\/pnas.1211205110","volume":"110","author":"S Takala-Harrison","year":"2013","unstructured":"Takala-Harrison, S. et al. Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia. Proc Natl Acad Sci USA 110, 240\u2013245, https:\/\/doi.org\/10.1073\/pnas.1211205110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"30593_CR13","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/nature12876","volume":"505","author":"F Ariey","year":"2014","unstructured":"Ariey, F. et al. A molecular marker of artemisinin-resistant Plasmodium falciparum malaria. Nature 505, 50\u201355, https:\/\/doi.org\/10.1038\/nature12876 (2014).","journal-title":"Nature"},{"key":"30593_CR14","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1126\/science.1260867","volume":"347","author":"J Straimer","year":"2015","unstructured":"Straimer, J. et al. Drug resistance. K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates. Science 347, 428\u2013431, https:\/\/doi.org\/10.1126\/science.1260867 (2015).","journal-title":"Science"},{"key":"30593_CR15","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/nbt.2925","volume":"32","author":"M Ghorbal","year":"2014","unstructured":"Ghorbal, M. et al. Genome editing in the human malaria parasite Plasmodium falciparum using the CRISPR-Cas9 system. Nat Biotechnol 32, 819\u2013821, https:\/\/doi.org\/10.1038\/nbt.2925 (2014).","journal-title":"Nat Biotechnol"},{"key":"30593_CR16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.mehy.2016.02.022","volume":"90","author":"P Wilairat","year":"2016","unstructured":"Wilairat, P., Kumpornsin, K. & Chookajorn, T. Plasmodium falciparum malaria: Convergent evolutionary trajectories towards delayed clearance following artemisinin treatment. Med Hypotheses 90, 19\u201322, https:\/\/doi.org\/10.1016\/j.mehy.2016.02.022 (2016).","journal-title":"Med Hypotheses"},{"key":"30593_CR17","doi-asserted-by":"publisher","unstructured":"Miotto, O. et al. Genetic architecture of artemisinin-resistant Plasmodium falciparum. Nat Genet, https:\/\/doi.org\/10.1038\/ng.3189 (2015).","DOI":"10.1038\/ng.3189"},{"key":"30593_CR18","doi-asserted-by":"publisher","unstructured":"Hott, A., Tucker, M. S., Casandra, D., Sparks, K. & Kyle, D. E. Fitness of artemisinin-resistant Plasmodium falciparum in vitro. J Antimicrob Chemother, https:\/\/doi.org\/10.1093\/jac\/dkv199 (2015).","DOI":"10.1093\/jac\/dkv199"},{"key":"30593_CR19","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1093\/molbev\/msu140","volume":"31","author":"K Kumpornsin","year":"2014","unstructured":"Kumpornsin, K. et al. Origin of robustness in generating drug-resistant malaria parasites. Mol Biol Evol 31, 1649\u20131660, https:\/\/doi.org\/10.1093\/molbev\/msu140 (2014).","journal-title":"Mol Biol Evol"},{"key":"30593_CR20","doi-asserted-by":"publisher","first-page":"3156","DOI":"10.1128\/AAC.00197-15","volume":"59","author":"A Hott","year":"2015","unstructured":"Hott, A. et al. Artemisinin-resistant Plasmodium falciparum parasites exhibit altered patterns of development in infected erythrocytes. Antimicrob Agents Chemother 59, 3156\u20133167, https:\/\/doi.org\/10.1128\/AAC.00197-15 (2015).","journal-title":"Antimicrob Agents Chemother"},{"key":"30593_CR21","doi-asserted-by":"publisher","first-page":"5392","DOI":"10.1073\/pnas.1218412110","volume":"110","author":"M Chugh","year":"2013","unstructured":"Chugh, M. et al. Protein complex directs hemoglobin-to-hemozoin formation in Plasmodium falciparum. Proc Natl Acad Sci USA 110, 5392\u20135397, https:\/\/doi.org\/10.1073\/pnas.1218412110 (2013).","journal-title":"Proc Natl Acad Sci USA"},{"key":"30593_CR22","doi-asserted-by":"publisher","first-page":"11405","DOI":"10.1073\/pnas.1104063108","volume":"108","author":"N Klonis","year":"2011","unstructured":"Klonis, N. et al. Artemisinin activity against Plasmodium falciparum requires hemoglobin uptake and digestion. Proc Natl Acad Sci USA 108, 11405\u201311410, https:\/\/doi.org\/10.1073\/pnas.1104063108 (2011).","journal-title":"Proc Natl Acad Sci USA"},{"key":"30593_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10111","volume":"6","author":"J Wang","year":"2015","unstructured":"Wang, J. et al. Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum. Nat Commun 6, 10111, https:\/\/doi.org\/10.1038\/ncomms10111 (2015).","journal-title":"Nat Commun"},{"key":"30593_CR24","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1128\/mr.60.2.301-315.1996","volume":"60","author":"SR Meshnick","year":"1996","unstructured":"Meshnick, S. R., Taylor, T. E. & Kamchonwongpaisan, S. Artemisinin and the antimalarial endoperoxides: from herbal remedy to targeted chemotherapy. Microbiol Rev 60, 301\u2013315 (1996).","journal-title":"Microbiol Rev"},{"key":"30593_CR25","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1126\/science.1260403","volume":"347","author":"S Mok","year":"2015","unstructured":"Mok, S. et al. Drug resistance. Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance. Science 347, 431\u2013435, https:\/\/doi.org\/10.1126\/science.1260403 (2015).","journal-title":"Population transcriptomics of human malaria parasites reveals the mechanism of artemisinin resistance. Science"},{"key":"30593_CR26","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1016\/j.cell.2014.07.011","volume":"158","author":"AM Lisewski","year":"2014","unstructured":"Lisewski, A. M. et al. Supergenomic Network Compression and the Discovery of EXP1 as a Glutathione Transferase Inhibited by Artesunate. Cell 158, 916\u2013928, https:\/\/doi.org\/10.1016\/j.cell.2014.07.011 (2014).","journal-title":"Cell"},{"key":"30593_CR27","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-10-339","volume":"10","author":"JA Flegg","year":"2011","unstructured":"Flegg, J. A., Guerin, P. J., White, N. J. & Stepniewska, K. Standardizing the measurement of parasite clearance in falciparum malaria: the parasite clearance estimator. Malar J 10, 339, https:\/\/doi.org\/10.1186\/1475-2875-10-339 (2011).","journal-title":"Malar J"},{"key":"30593_CR28","doi-asserted-by":"publisher","first-page":"e31938","DOI":"10.1371\/journal.pone.0031938","volume":"7","author":"M Poreba","year":"2012","unstructured":"Poreba, M. et al. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum. PLoS One 7, e31938, https:\/\/doi.org\/10.1371\/journal.pone.0031938 (2012).","journal-title":"PLoS One"},{"key":"30593_CR29","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1016\/j.tibs.2009.08.004","volume":"35","author":"TS Skinner-Adams","year":"2010","unstructured":"Skinner-Adams, T. S. et al. Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials. Trends Biochem Sci 35, 53\u201361, https:\/\/doi.org\/10.1016\/j.tibs.2009.08.004 (2010).","journal-title":"Trends Biochem Sci"},{"key":"30593_CR30","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-016-1097-9","volume":"15","author":"P Ponsuwanna","year":"2016","unstructured":"Ponsuwanna, P. et al. Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites. Malar J 15, 51, https:\/\/doi.org\/10.1186\/s12936-016-1097-9 (2016).","journal-title":"Malar J"},{"key":"30593_CR31","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.gene.2009.09.003","volume":"449","author":"I Cambra","year":"2010","unstructured":"Cambra, I., Garcia, F. J. & Martinez, M. Clan CD of cysteine peptidases as an example of evolutionary divergences in related protein families across plant clades. Gene 449, 59\u201369, https:\/\/doi.org\/10.1016\/j.gene.2009.09.003 (2010).","journal-title":"Gene"},{"key":"30593_CR32","doi-asserted-by":"publisher","unstructured":"Hirano, T. Chromosome Dynamics during Mitosis. Cold Spring Harb Perspect Biol 7, https:\/\/doi.org\/10.1101\/cshperspect.a015792 (2015).","DOI":"10.1101\/cshperspect.a015792"},{"key":"30593_CR33","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/S1471-4922(03)00038-2","volume":"19","author":"JC Mottram","year":"2003","unstructured":"Mottram, J. C., Helms, M. J., Coombs, G. H. & Sajid, M. Clan CD cysteine peptidases of parasitic protozoa. Trends Parasitol 19, 182\u2013187 (2003).","journal-title":"Trends Parasitol"},{"key":"30593_CR34","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/S1473-3099(16)30409-1","volume":"17","author":"R Amato","year":"2017","unstructured":"Amato, R. et al. Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study. Lancet Infect Dis 17, 164\u2013173, https:\/\/doi.org\/10.1016\/S1473-3099(16)30409-1 (2017).","journal-title":"Lancet Infect Dis"},{"key":"30593_CR35","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/S1473-3099(16)30415-7","volume":"17","author":"B Witkowski","year":"2017","unstructured":"Witkowski, B. et al. A surrogate marker of piperaquine-resistant Plasmodium falciparum malaria: a phenotype-genotype association study. Lancet Infect Dis 17, 174\u2013183, https:\/\/doi.org\/10.1016\/S1473-3099(16)30415-7 (2017).","journal-title":"Lancet Infect Dis"},{"key":"30593_CR36","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1093\/molbev\/msw037","volume":"33","author":"SJ Gabryszewski","year":"2016","unstructured":"Gabryszewski, S. J., Modchang, C., Musset, L., Chookajorn, T. & Fidock, D. A. Combinatorial Genetic Modeling of pfcrt-Mediated Drug Resistance Evolution in Plasmodium falciparum. Mol Biol Evol 33, 1554\u20131570, https:\/\/doi.org\/10.1093\/molbev\/msw037 (2016).","journal-title":"Mol Biol Evol"},{"key":"30593_CR37","doi-asserted-by":"publisher","first-page":"244","DOI":"10.4161\/viru.2.3.16194","volume":"2","author":"T Chookajorn","year":"2011","unstructured":"Chookajorn, T. & Kumpornsin, K. \u2018Snakes and Ladders\u2019 of drug resistance evolution. Virulence 2, 244\u2013247 (2011).","journal-title":"Virulence"},{"key":"30593_CR38","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/sj.hdy.6800915","volume":"100","author":"MA Felix","year":"2008","unstructured":"Felix, M. A. & Wagner, A. Robustness and evolution: concepts, insights and challenges from a developmental model system. Heredity (Edinb) 100, 132\u2013140, https:\/\/doi.org\/10.1038\/sj.hdy.6800915 (2008).","journal-title":"Heredity (Edinb)"},{"key":"30593_CR39","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.tig.2009.07.005","volume":"25","author":"J Masel","year":"2009","unstructured":"Masel, J. & Siegal, M. L. Robustness: mechanisms and consequences. Trends Genet 25, 395\u2013403 (2009).","journal-title":"Trends Genet"},{"key":"30593_CR40","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nrg1471","volume":"5","author":"H Kitano","year":"2004","unstructured":"Kitano, H. Biological robustness. Nat Rev Genet 5, 826\u2013837, https:\/\/doi.org\/10.1038\/nrg1471 (2004).","journal-title":"Nat Rev Genet"},{"key":"30593_CR41","doi-asserted-by":"publisher","first-page":"e1000243","DOI":"10.1371\/journal.pgen.1000243","volume":"4","author":"S Nair","year":"2008","unstructured":"Nair, S. et al. Adaptive copy number evolution in malaria parasites. PLoS Genet 4, e1000243 (2008).","journal-title":"PLoS Genet"},{"key":"30593_CR42","doi-asserted-by":"publisher","first-page":"e57","DOI":"10.1371\/journal.ppat.0020057","volume":"2","author":"C Kidgell","year":"2006","unstructured":"Kidgell, C. et al. A systematic map of genetic variation in Plasmodium falciparum. PLoS Pathog 2, e57 (2006).","journal-title":"PLoS Pathog"},{"key":"30593_CR43","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1093\/molbev\/msu397","volume":"32","author":"IH Cheeseman","year":"2015","unstructured":"Cheeseman, I. H. et al. Pooled sequencing and rare variant association tests for identifying the determinants of emerging drug resistance in malaria parasites. Mol Biol Evol 32, 1080\u20131090, https:\/\/doi.org\/10.1093\/molbev\/msu397 (2015).","journal-title":"Mol Biol Evol"},{"key":"30593_CR44","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1073\/pnas.1600459113","volume":"113","author":"HM Ismail","year":"2016","unstructured":"Ismail, H. M. et al. Artemisinin activity-based probes identify multiple molecular targets within the asexual stage of the malaria parasites Plasmodium falciparum 3D7. Proc Natl Acad Sci USA 113, 2080\u20132085, https:\/\/doi.org\/10.1073\/pnas.1600459113 (2016).","journal-title":"Proc Natl Acad Sci USA"},{"key":"30593_CR45","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/nature14412","volume":"520","author":"A Mbengue","year":"2015","unstructured":"Mbengue, A. et al. A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature 520, 683\u2013687, https:\/\/doi.org\/10.1038\/nature14412 (2015).","journal-title":"Nature"},{"key":"30593_CR46","doi-asserted-by":"publisher","first-page":"e1002132","DOI":"10.1371\/journal.pbio.1002132","volume":"13","author":"C Dogovski","year":"2015","unstructured":"Dogovski, C. et al. Targeting the cell stress response of Plasmodium falciparum to overcome artemisinin resistance. PLoS Biol 13, e1002132, https:\/\/doi.org\/10.1371\/journal.pbio.1002132 (2015).","journal-title":"PLoS Biol"},{"key":"30593_CR47","doi-asserted-by":"publisher","first-page":"e1000339","DOI":"10.1371\/journal.pcbi.1000339","volume":"5","author":"JM Mauritz","year":"2009","unstructured":"Mauritz, J. M. et al. The homeostasis of Plasmodium falciparum-infected red blood cells. PLoS Comput Biol 5, e1000339, https:\/\/doi.org\/10.1371\/journal.pcbi.1000339 (2009).","journal-title":"PLoS Comput Biol"},{"key":"30593_CR48","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1126\/science.781840","volume":"193","author":"W Trager","year":"1976","unstructured":"Trager, W. & Jensen, J. B. Human malaria parasites in continuous culture. Science 193, 673\u2013675 (1976).","journal-title":"Science"},{"key":"30593_CR49","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.1128\/IAI.66.6.2969-2975.1998","volume":"66","author":"V Fernandez","year":"1998","unstructured":"Fernandez, V., Treutiger, C. J., Nash, G. B. & Wahlgren, M. Multiple adhesive phenotypes linked to rosetting binding of erythrocytes in Plasmodium falciparum malaria. Infect Immun 66, 2969\u20132975 (1998).","journal-title":"Infect Immun"},{"key":"30593_CR50","doi-asserted-by":"publisher","first-page":"418","DOI":"10.2307\/3280287","volume":"65","author":"C Lambros","year":"1979","unstructured":"Lambros, C. & Vanderberg, J. P. Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol 65, 418\u2013420 (1979).","journal-title":"J Parasitol"},{"key":"30593_CR51","doi-asserted-by":"publisher","first-page":"17017","DOI":"10.1038\/nmicrobiol.2017.17","volume":"2","author":"M Ganter","year":"2017","unstructured":"Ganter, M. et al. Plasmodium falciparum CRK4 directs continuous rounds of DNA replication during schizogony. Nat Microbiol 2, 17017, https:\/\/doi.org\/10.1038\/nmicrobiol.2017.17 (2017).","journal-title":"Nat Microbiol"},{"key":"30593_CR52","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1073\/pnas.0806926106","volume":"106","author":"I Russo","year":"2009","unstructured":"Russo, I., Oksman, A., Vaupel, B. & Goldberg, D. E. A calpain unique to alveolates is essential in Plasmodium falciparum and its knockdown reveals an involvement in pre-S-phase development. Proc Natl Acad Sci USA 106, 1554\u20131559, https:\/\/doi.org\/10.1073\/pnas.0806926106 (2009).","journal-title":"Proc Natl Acad Sci USA"},{"key":"30593_CR53","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.1002\/cyto.a.20972","volume":"77","author":"M Theron","year":"2010","unstructured":"Theron, M., Hesketh, R. L., Subramanian, S. & Rayner, J. C. An adaptable two-color flow cytometric assay to quantitate the invasion of erythrocytes by Plasmodium falciparum parasites. Cytometry A 77, 1067\u20131074, https:\/\/doi.org\/10.1002\/cyto.a.20972 (2010).","journal-title":"Cytometry A"},{"key":"30593_CR54","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1016\/j.exppara.2008.10.008","volume":"121","author":"S Izumiyama","year":"2009","unstructured":"Izumiyama, S., Omura, M., Takasaki, T., Ohmae, H. & Asahi, H. Plasmodium falciparum: development and validation of a measure of intraerythrocytic growth using SYBR Green I in a flow cytometer. Exp Parasitol 121, 144\u2013150, https:\/\/doi.org\/10.1016\/j.exppara.2008.10.008 (2009).","journal-title":"Exp Parasitol"},{"key":"30593_CR55","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1128\/aem.56.6.1875-1881.1990","volume":"56","author":"M Zwietering","year":"1990","unstructured":"Zwietering, M., Jongenburger, I., Rombouts, F. & Van\u2019t Riet, K. Modeling of the bacterial growth curve. Applied and environmental microbiology 56, 1875\u20131881 (1990).","journal-title":"Applied and environmental microbiology"},{"key":"30593_CR56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1073\/pnas.18.1.1","volume":"18","author":"CP Winsor","year":"1932","unstructured":"Winsor, C. P. The Gompertz curve as a growth curve. Proceedings of the national academy of sciences 18, 1\u20138 (1932).","journal-title":"Proceedings of the national academy of sciences"},{"key":"30593_CR57","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1002\/cyto.a.22620","volume":"87","author":"HD Summers","year":"2015","unstructured":"Summers, H. D., Wills, J. W., Brown, M. R. & Rees, P. Poisson-event-based analysis of cell proliferation. Cytometry A 87, 385\u2013392, https:\/\/doi.org\/10.1002\/cyto.a.22620 (2015).","journal-title":"Cytometry A"},{"key":"30593_CR58","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81, 559\u2013575, https:\/\/doi.org\/10.1086\/519795 (2007).","journal-title":"Am J Hum Genet"},{"key":"30593_CR59","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1038\/nmeth.1681","volume":"8","author":"C Lippert","year":"2011","unstructured":"Lippert, C. et al. FaST linear mixed models for genome-wide association studies. Nat Methods 8, 833\u2013835, https:\/\/doi.org\/10.1038\/nmeth.1681 (2011).","journal-title":"Nat Methods"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30593-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30593-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30593-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T08:43:27Z","timestamp":1671612207000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-30593-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,22]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["30593"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-30593-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,22]]},"assertion":[{"value":"3 April 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 August 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"12622"}}