{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:38:06Z","timestamp":1790746686903,"version":"4.1.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T00:00:00Z","timestamp":1545609600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,12,24]],"date-time":"2018-12-24T00:00:00Z","timestamp":1545609600000},"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>\n                  <jats:p>\n                    Glucose is an essential nutrient for\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    and robust glycolytic activity is indicative of viable parasites. Using NMR spectroscopy, we show that\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    infected erythrocytes consume ~20 times more glucose, and trophozoites metabolize ~6 times more glucose than ring stage parasites. The glycolytic activity, and hence parasite viability, can be measured within a period of 2\u2009h to 5\u2009h, using this method. This facilitates antimalarial bioactivity screening on ring and trophozoite stage parasites, exclusively. We demonstrate this using potent and mechanistically distinct antimalarial compounds such as chloroquine, atovaquone, cladosporin, DDD107498 and artemisinin. Our findings indicate that ring stage parasites are inherently more tolerant to antimalarial inhibitors, a feature which may facilitate emergence of drug resistance. Thus, there is a need to discover novel antimalarial compounds, which are potent and fast acting against ring stage parasites. The NMR method reported here can facilitate the identification of such molecules.\n                  <\/jats:p>","DOI":"10.1038\/s41598-018-36197-3","type":"journal-article","created":{"date-parts":[[2018,12,20]],"date-time":"2018-12-20T12:27:36Z","timestamp":1545308856000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Evaluating antimalarial efficacy by tracking glycolysis in Plasmodium falciparum using NMR spectroscopy"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3341-4846","authenticated-orcid":false,"given":"Rupali","family":"Shivapurkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tejashri","family":"Hingamire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay S.","family":"Kulkarni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Rajamohanan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Srinivasa","family":"Reddy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhanasekaran","family":"Shanmugam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,12,24]]},"reference":[{"key":"36197_CR1","unstructured":"WHO World Malaria Report, http:\/\/www.who.int\/malaria\/publications\/world-malaria-report-2017\/en\/ (2017)."},{"key":"36197_CR2","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/nm.3073","volume":"19","author":"LH Miller","year":"2013","unstructured":"Miller, L. H., Ackerman, H. C., Su, X.-Z. & Wellems, T. E. Malaria biology and disease pathogenesis: insights for new treatments. Nat. Med. 19, 156\u2013167 (2013).","journal-title":"Nat. Med."},{"key":"36197_CR3","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.pt.2014.02.001","volume":"30","author":"JE Salcedo-Sora","year":"2014","unstructured":"Salcedo-Sora, J. E., Caamano-Gutierrez, E., Ward, S. A. & Biagini, G. A. The proliferating cell hypothesis: a metabolic framework for Plasmodium growth and development. Trends Parasitol. 30, 170\u2013175 (2014).","journal-title":"Trends Parasitol."},{"key":"36197_CR4","doi-asserted-by":"publisher","first-page":"634","DOI":"10.1111\/febs.13615","volume":"283","author":"DD van Niekerk","year":"2016","unstructured":"van Niekerk, D. D., Penkler, G. P., du Toit, F. & Snoep, J. L. Targeting glycolysis in the malaria parasite Plasmodium falciparum. FEBS. J. 283, 634\u2013646 (2016).","journal-title":"FEBS. J."},{"key":"36197_CR5","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1124\/jpet.108.141929","volume":"327","author":"DA van Schalkwyk","year":"2008","unstructured":"van Schalkwyk, D. A., Priebe, W. & Saliba, K. J. The inhibitory effect of 2-halo derivatives of D-glucose on glycolysis and on the proliferation of the human malaria parasite Plasmodium falciparum. J. Pharmacol. Exp. Ther. 327, 511\u2013517 (2008).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"36197_CR6","doi-asserted-by":"publisher","first-page":"6151","DOI":"10.1016\/j.febslet.2005.09.088","volume":"579","author":"M Mehta","year":"2005","unstructured":"Mehta, M., Sonawat, H. M. & Sharma, S. Malaria parasite-infected erythrocytes inhibit glucose utilization in uninfected red cells. FEBS. Lett. 579, 6151\u20136158 (2005).","journal-title":"FEBS. Lett."},{"key":"36197_CR7","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. of Sci. USA 110, 5157\u20135162 (2013).","journal-title":"Proc. Natl. Acad. of Sci. USA"},{"key":"36197_CR8","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1086\/656476","volume":"202","author":"F Teuscher","year":"2010","unstructured":"Teuscher, F. et al. Artemisinin induced dormancy in Plasmodium falciparum: Duration, recovery rates and implications in treatment failure. J. Infect. Dis. 202, 1362\u20131368 (2010).","journal-title":"J. Infect. Dis."},{"key":"36197_CR9","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1128\/AAC.05456-11","volume":"56","author":"F Teuscher","year":"2012","unstructured":"Teuscher, F., Chen, N., Kyle, D. E., Gatton, M. L. & Cheng, Q. Phenotypic changes in artemisinin-resistant Plasmodium falciparum lines in vitro: evidence for decreased sensitivity to dormancy and growth inhibition. Antimicrob. Agents and Chemother. 56, 428\u2013431 (2012).","journal-title":"Antimicrob. Agents and Chemother."},{"key":"36197_CR10","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.1128\/AAC.48.5.1807-1810.2004","volume":"48","author":"TN Bennett","year":"2004","unstructured":"Bennett, T. N. et al. Novel, rapid, and inexpensive cell-based quantification of antimalarial drug efficacy. Antimicrob. Agents and Chemother. 48, 1807\u20131810 (2004).","journal-title":"Antimicrob. Agents and Chemother."},{"key":"36197_CR11","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1128\/AAC.01144-06","volume":"51","author":"ML Baniecki","year":"2007","unstructured":"Baniecki, M. L., Wirth, D. F. & Clardy, J. High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Antimicrob. Agents and Chemother. 51, 716\u2013723 (2007).","journal-title":"Antimicrob. Agents and Chemother."},{"key":"36197_CR12","doi-asserted-by":"publisher","first-page":"577","DOI":"10.2307\/3281373","volume":"69","author":"TG Geary","year":"1983","unstructured":"Geary, T. G., Divo, A. A. & Jensen, J. B. An in vitro assay system for the identification of potential antimalarial drugs. J. Parasitol. 69, 577\u2013583 (1983).","journal-title":"J. Parasitol."},{"key":"36197_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-8-294","volume":"8","author":"S Karl","year":"2009","unstructured":"Karl, S., Wong, R. P., St Pierre, T. G. & Davis, T. M. A comparative study of a flow-cytometry-based assessment of in vitro Plasmodium falciparum drug sensitivity. Malar. J. 8, 294 (2009).","journal-title":"Malar. J."},{"key":"36197_CR14","doi-asserted-by":"publisher","first-page":"2308","DOI":"10.1101\/gr.2523904","volume":"14","author":"KG Le Roch","year":"2004","unstructured":"Le Roch, K. G. et al. Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle. Genome. Res. 14, 2308\u20132318 (2004).","journal-title":"Genome. Res."},{"key":"36197_CR15","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.molbiopara.2010.09.001","volume":"175","author":"KL Olszewski","year":"2011","unstructured":"Olszewski, K. L. & Llin\u00e1s, M. Central carbon metabolism of Plasmodium parasites. Mol. Biochem. Parasitol. 175, 95\u2013103 (2011).","journal-title":"Mol. Biochem. Parasitol."},{"key":"36197_CR16","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/0163-7258(93)90056-J","volume":"57","author":"AFG Slater","year":"1993","unstructured":"Slater, A. F. G. Chloroquine: Mechanism of drug action and resistance in Plasmodium falciparum. Pharmacol. Ther. 57, 203\u2013235 (1993).","journal-title":"Pharmacol. Ther."},{"key":"36197_CR17","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1126\/science.3887571","volume":"228","author":"D Klayman","year":"1985","unstructured":"Klayman, D. Qinghaosu (artemisinin): an antimalarial drug from China. Science 228, 1049\u20131055 (1985).","journal-title":"Science"},{"key":"36197_CR18","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1093\/jac\/36.6.1073","volume":"36","author":"PL Chiodini","year":"1995","unstructured":"Chiodini, P. L. et al. Evaluation of atovaquone in the treatment of patients with uncomplicated Plasmodium falciparum malaria. J. Antimicrob. Chemother. 36, 1073\u20131078 (1995).","journal-title":"J. Antimicrob. Chemother."},{"key":"36197_CR19","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1038\/nature14451","volume":"522","author":"B Baraga\u00f1a","year":"2015","unstructured":"Baraga\u00f1a, B. et al. A novel multiple-stage antimalarial agent that inhibits protein synthesis. Nature 522, 315\u2013320 (2015).","journal-title":"Nature"},{"key":"36197_CR20","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1016\/j.chom.2012.04.015","volume":"11","author":"D Hoepfner","year":"2012","unstructured":"Hoepfner, D. et al. Selective and specific inhibition of the Plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin. Cell Host Microbe 11, 654\u2013663 (2012).","journal-title":"Cell Host Microbe"},{"key":"36197_CR21","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1016\/j.bmcl.2013.03.067","volume":"23","author":"MA Biamonte","year":"2013","unstructured":"Biamonte, M. A., Wanner, J. & Le Roch, K. G. Recent advances in malaria drug discovery. Bioorg. Med. Chem. Lett. 23, 2829\u20132843 (2013).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"36197_CR22","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/nrmicro.2017.161","volume":"16","author":"K Haldar","year":"2018","unstructured":"Haldar, K., Bhattacharjee, S. & Safeukui, I. Drug resistance in Plasmodium. Nat. Rev. Microbiol. 16, 156\u2013170 (2018).","journal-title":"Nat. Rev. Microbiol."},{"key":"36197_CR23","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1046\/j.1365-2958.1999.01515.x","volume":"33","author":"IK Srivastava","year":"1999","unstructured":"Srivastava, I. K., Morrisey, J. M., Darrouzet, E., Daldal, F. & Vaidya, A. B. Resistance mutations revel the atovaquone-binding domain of cytochrome b in malaria parasites. Mol. Microbiol. 33, 704\u2013711 (1999).","journal-title":"Mol. Microbiol."},{"key":"36197_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/1475-2875-3-24","volume":"3","author":"AM Talman","year":"2004","unstructured":"Talman, A. M., Domarle, O., McKenzie, F. E., Fr\u00e9d\u00e9ric, A. & Vincent, R. Gametocytogenesis: the puberty of Plasmodium falciparum. Malar. J. 3, 24 (2004).","journal-title":"Malar. J."},{"key":"36197_CR25","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nm.4381","volume":"23","author":"B Blasco","year":"2017","unstructured":"Blasco, B., Leroy, D. & Fidock, D. A. Antimalarial drug resistance: linking Plasmodium falciparum parasite biology to the clinic. Nat. med. 23, 917\u2013928 (2017).","journal-title":"Nat. med."},{"key":"36197_CR26","first-page":"453","volume":"16","author":"EJ Roth","year":"1990","unstructured":"Roth, E. J. Plasmodium falciparum carbohydrate metabolism: a connection between host cell and parasite. Blood Cells 16, 453\u2013460 (1990).","journal-title":"Blood Cells"},{"key":"36197_CR27","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.chom.2009.01.004","volume":"5","author":"KL Olszewski","year":"2009","unstructured":"Olszewski, K. L. et al. Host-parasite interactions revealed by Plasmodium falciparum metabolomics. Cell Host Microbe. 5, 191\u2013199 (2009).","journal-title":"Cell Host Microbe."},{"key":"36197_CR28","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.1038\/nprot.2009.198","volume":"4","author":"A Radfar","year":"2009","unstructured":"Radfar, A. et al. Synchronous culture of Plasmodium falciparum at high parasitemia levels. Nat. Protoc. 4, 1899\u20131915 (2009).","journal-title":"Nat. Protoc."},{"key":"36197_CR29","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1111\/j.1550-7408.1983.tb02932.x","volume":"30","author":"EM Rivadeneira","year":"1983","unstructured":"Rivadeneira, E. M., Wasserman, M. & Espinal, C. T. Separation and concentration of schizonts of Plasmodium falciparum by Percoll gradients. J. Protozool. 30, 367\u2013370 (1983).","journal-title":"J. Protozool."},{"key":"36197_CR30","doi-asserted-by":"crossref","unstructured":"Smilkstein, M., Sriwilaijaroen, N., Kelly, J. X., Wilairat, P., Riscoe, M. Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrob. Agents Chemother. 48, 1803\u20131806 (2004).","DOI":"10.1128\/AAC.48.5.1803-1806.2004"},{"key":"36197_CR31","doi-asserted-by":"crossref","unstructured":"Lloyd, S. G., Zeng, H., Wang, P., Chatham, J. C. Lactate isotopomer analysis by 1H NMR spectroscopy: consideration of long-range nuclear spin-spin interactions. Magn. Reson. Med. 51, 1279\u20131282 (2004).","DOI":"10.1002\/mrm.20075"},{"key":"36197_CR32","unstructured":"Pomin, V. H. Unravelling Glycobiology by NMR Spectroscopy., Glycosylation (Chapter. 04, Page 63\u201398). (ed Stefana Petrescu) (InTech, 2012)."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36197-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36197-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36197-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T07:23:57Z","timestamp":1671607437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-36197-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,24]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["36197"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-36197-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,24]]},"assertion":[{"value":"16 August 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 December 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":"18076"}}