{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T02:51:14Z","timestamp":1789267874315,"version":"build-2803163510"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Drug resistance in <jats:italic>Plasmodium falciparum<\/jats:italic> presents a formidable challenge to the humanity. And, unavailability of an effective vaccine worsens the situation further. Autophagy is one of the mechanisms employed by parasite to evade drug pressure to survive. Autophagy induced by the <jats:italic>P. falciparum<\/jats:italic> in response to the oleuropein pressure may answer many questions related to the parasite survival as well as evolving drug tolerance. The survival\/autophagy axis could be an important avenue to explore in order to address certain questions related to the evolution of drug resistance. In addition, humanized mouse model of <jats:italic>P. falciparum<\/jats:italic> infection could serve as an important preclinical tool to investigate the oleuropein-induced autophagy, potentially helping to dissect the mechanisms underlying the development of antimalarial drug resistance.<\/jats:p>","DOI":"10.3389\/fmicb.2024.1453998","type":"journal-article","created":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T11:57:46Z","timestamp":1724155066000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Oleuropein mediated autophagy begets antimalarial drug resistance"],"prefix":"10.3389","volume":"15","author":[{"given":"Prakriti","family":"Sharma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil Roy","family":"Chaudhary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Devi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushmita","family":"Negi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikunj","family":"Tandel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev K.","family":"Tyagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1111\/mmi.14441","article-title":"Autophagy-related protein PfATG18 participates in food vacuole dynamics and autophagy-like pathway in Plasmodium falciparum","volume":"113","author":"Agrawal","year":"2020","journal-title":"Mol. Microbiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e18045","DOI":"10.1371\/journal.pone.0018045","article-title":"Further improvements of the P. falciparum humanized mouse model","volume":"6","author":"Arnold","year":"2011","journal-title":"PLoS ONE"},{"key":"B3","doi-asserted-by":"publisher","first-page":"173509","DOI":"10.1016\/j.ejphar.2020.173509","article-title":"The effect of oleuropein on apoptotic pathway regulators in breast cancer cells","volume":"886","author":"Asgharzade","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"903","DOI":"10.1038\/nbt1326","article-title":"Robust expansion of human hepatocytes in Fah-\/-\/Rag2-\/-\/Il2rg-\/- mice","volume":"25","author":"Azuma","year":"2007","journal-title":"Nat. Biotechnol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/0169-4758(95)80147-2","article-title":"Human Plasmodium liver stages in SCID mice: a feasible model?","volume":"11","author":"Badell","year":"1995","journal-title":"Parasitol. Today"},{"key":"B6","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.molbiopara.2012.09.008","article-title":"Apicoplast triose phosphate transporter (TPT) gene knockout is lethal for Plasmodium","volume":"186","author":"Banerjee","year":"2012","journal-title":"Mol. Biochem. Parasitol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"20507","DOI":"10.1073\/pnas.0710528105","article-title":"Repopulation of adult and neonatal mice with human hepatocytes: a chimeric animal model","volume":"104","author":"Bissig","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B8","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.lfs.2016.06.030","article-title":"Understanding the biology of the Plasmodium falciparum apicoplast; an excellent target for antimalarial drug development","volume":"158","author":"Chakraborty","year":"2016","journal-title":"Life Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/0952-7915(94)90107-4","article-title":"Probing immune functions in RAG-deficient mice","volume":"6","author":"Chen","year":"1994","journal-title":"Curr. Opin. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"21783","DOI":"10.1073\/pnas.0912274106","article-title":"Expression of human cytokines dramatically improves reconstitution of specific human-blood lineage cells in humanized mice","volume":"106","author":"Chen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B11","doi-asserted-by":"publisher","first-page":"31206","DOI":"10.3390\/ijms23031206","article-title":"Oleacein attenuates lipopolysaccharide-induced inflammation in THP-1-derived macrophages by the inhibition of TLR4\/MyD88\/NF-kappaB pathway","volume":"23","author":"Cirmi","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.4049\/jimmunol.162.5.2761","article-title":"Dissecting NK cell development using a novel alymphoid mouse model: investigating the role of the c-abl proto-oncogene in murine NK cell differentiation","volume":"162","author":"Colucci","year":"1999","journal-title":"J. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1042\/bse0510127","article-title":"Metamorphoses of malaria: the role of autophagy in parasite differentiation","volume":"51","author":"Coppens","year":"2011","journal-title":"Essays Biochem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.bbrc.2011.01.042","article-title":"The reconstituted \u201chumanized liver\u201d in TK-NOG mice is mature and functional","volume":"405","author":"Hasegawa","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B15","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1007\/s40471-021-00266-5","article-title":"Antimalarial drug resistance and implications for the WHO global technical strategy","volume":"8","author":"Ippolito","year":"2021","journal-title":"Curr. Epidemiol. Rep."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1182\/blood-2001-12-0207","article-title":"NOD\/SCID\/gamma(c)(null) mouse: an excellent recipient mouse model for engraftment of human cells","volume":"100","author":"Ito","year":"2002","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/s41420-018-0107-9","article-title":"Basal and starvation-induced autophagy mediates parasite survival during intraerythrocytic stages of Plasmodium falciparum","volume":"4","author":"Joy","year":"2018","journal-title":"Cell Death Discov."},{"key":"B18","doi-asserted-by":"publisher","first-page":"e0026922","DOI":"10.1128\/aac.00269-22","article-title":"An alternative autophagy-related mechanism of chloroquine drug resistance in the malaria parasite","volume":"66","author":"Kamil","year":"2022","journal-title":"Antimicrob. Agents Chemother."},{"key":"B19","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41420-023-01401-5","article-title":"Cytoprotective autophagy as a pro-survival strategy in ART-resistant malaria parasites","volume":"9","author":"Kannan","year":"2023","journal-title":"Cell Death Discov."},{"key":"B20","doi-asserted-by":"publisher","first-page":"30415","DOI":"10.3390\/life12030415","article-title":"Autophagy pathways in the genesis of Plasmodium-derived microvesicles: a double-edged sword?","volume":"12","author":"Leleu","year":"2022","journal-title":"Life"},{"key":"B21","doi-asserted-by":"publisher","first-page":"e00805","DOI":"10.1016\/j.heliyon.2018.e00805","article-title":"In vitro antioxidant activity of olive leaf extract (Olea europaea L.) and its protective effect on oxidative damage in human erythrocytes","volume":"4","author":"Lins","year":"2018","journal-title":"Heliyon"},{"key":"B22","doi-asserted-by":"publisher","first-page":"4504","DOI":"10.1002\/jcb.27738","article-title":"Oleuropein induces apoptosis via abrogating NF-kappaB activation cascade in estrogen receptor-negative breast cancer cells","volume":"120","author":"Liu","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1126\/science.2971269","article-title":"The SCID-hu mouse: murine model for the analysis of human hematolymphoid differentiation and function","volume":"241","author":"Mccune","year":"1988","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/0092-8674(92)90030-G","article-title":"RAG-1-deficient mice have no mature B and T lymphocytes","volume":"68","author":"Mombaerts","year":"1992","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1084\/jem.177.1.191","article-title":"Homozygous scid\/scid;beige\/beige mice have low levels of spontaneous or neonatal T cell-induced B cell generation","volume":"177","author":"Mosier","year":"1993","journal-title":"J. Exp. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"6311","DOI":"10.1038\/s41598-023-33176-1","article-title":"Population dynamics and drug resistance mutations in Plasmodium falciparum on the Bijag\u00f3s Archipelago, Guinea-Bissau","volume":"13","author":"Moss","year":"2023","journal-title":"Sci. Rep."},{"key":"B27","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.actatropica.2005.06.009","volume":"95","author":"Mutabingwa","year":"2005","journal-title":"Acta Trop."},{"key":"B28","doi-asserted-by":"publisher","first-page":"578","DOI":"10.3390\/antiox8120578","article-title":"Oleuropein, a bioactive compound from Olea europaea L., as a potential preventive and therapeutic agent in non-communicable diseases","volume":"8","author":"Nediani","year":"2019","journal-title":"Antioxidants"},{"key":"B29","doi-asserted-by":"publisher","first-page":"4568","DOI":"10.1038\/s41467-023-39914-3","article-title":"Preventing antimalarial drug resistance with triple artemisinin-based combination therapies","volume":"14","author":"Nguyen","year":"2023","journal-title":"Nat. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1017\/S001667230001404X","article-title":"Pigmentation and lysosome function in mice homozygous for both pale ear and beige-J pigment genes","volume":"35","author":"Novak","year":"1980","journal-title":"Genet. Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1016\/j.pt.2023.09.011","article-title":"The many paths to artemisinin resistance in Plasmodium falciparum","volume":"39","author":"Pandit","year":"2023","journal-title":"Trends Parasitol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1080\/15548627.2015.1067361","article-title":"Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms","volume":"11","author":"Prado","year":"2015","journal-title":"Autophagy"},{"key":"B33","doi-asserted-by":"publisher","first-page":"3290","DOI":"10.1073\/pnas.89.8.3290","article-title":"The nonobese diabetic scid mouse: model for spontaneous thymomagenesis associated with immunodeficiency","volume":"89","author":"Prochazka","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e0063022","DOI":"10.1128\/mbio.00630-22","article-title":"Autophagy underlies the proteostasis mechanisms of artemisinin resistance in P. falciparum Malaria","volume":"13","author":"Ray","year":"2022","journal-title":"mBio"},{"key":"B35","doi-asserted-by":"publisher","first-page":"35344","DOI":"10.18632\/oncotarget.6119","article-title":"Oleuropein aglycone induces autophagy via the AMPK\/mTOR signalling pathway: a mechanistic insight","volume":"6","author":"Rigacci","year":"2015","journal-title":"Oncotarget"},{"key":"B36","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/nrd2272","article-title":"Potential therapeutic applications of autophagy","volume":"6","author":"Rubinsztein","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"B37","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.pt.2022.04.004","article-title":"Plasmodium's fight for survival: escaping elimination while acquiring nutrients","volume":"38","author":"Schroeder","year":"2022","journal-title":"Trends Parasitol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"109463","DOI":"10.1016\/j.isci.2024.109463","article-title":"Oleuropein activates autophagy to circumvent anti-plasmodial defense","volume":"27","author":"Sharma","year":"2024","journal-title":"iScience"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4047","DOI":"10.2147\/IDR.S279433","article-title":"Antimalarial drug resistance and novel targets for antimalarial drug discovery","volume":"13","author":"Shibeshi","year":"2020","journal-title":"Infect. Drug Resist."},{"key":"B40","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/0092-8674(92)90029-C","article-title":"RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement","volume":"68","author":"Shinkai","year":"1992","journal-title":"Cell"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1097\/01.TP.0000083041.44829.2C","article-title":"NOD\/LtSz-Rag1nullPfpnull mice: a new model system with increased levels of human peripheral leukocyte and hematopoietic stem-cell engraftment","volume":"76","author":"Shultz","year":"2003","journal-title":"Transplantation"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1017\/S0031182021002134","article-title":"Current status of experimental models for the study of malaria","volume":"149","author":"Simwela","year":"2022","journal-title":"Parasitology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7690","DOI":"10.1038\/ncomms8690","article-title":"Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice","volume":"6","author":"Soulard","year":"2015","journal-title":"Nat. Commun."},{"key":"B44","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1111\/cmi.12524","article-title":"Host cell autophagy contributes to Plasmodium liver development","volume":"18","author":"Thieleke-Matos","year":"2016","journal-title":"Cell Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1016\/0264-410X(95)00081-B","article-title":"Establishment of a SCID mouse model having circulating human red blood cells and a possible growth of Plasmodium falciparum in the mouse","volume":"13","author":"Tsuji","year":"1995","journal-title":"Vaccine"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.2217\/imt-2021-0102","article-title":"Plasmodium falciparum-infected humanized mice: a viable preclinical tool","volume":"13","author":"Tyagi","year":"2021","journal-title":"Immunotherapy"},{"key":"B47","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1186\/s12916-018-1156-x","article-title":"High-level artemisinin-resistance with quinine co-resistance emerges in P. falciparum malaria under in vivo artesunate pressure","volume":"16","author":"Tyagi","year":"","journal-title":"BMC Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2550","DOI":"10.3389\/fimmu.2018.02550","article-title":"Humanized mice are instrumental to the study of Plasmodium falciparum infection","volume":"9","author":"Tyagi","year":"","journal-title":"Front. Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1128\/mBio.02021-17","article-title":"ATG8 is essential specifically for an autophagy-independent function in apicoplast biogenesis in blood-stage malaria parasites","volume":"9","author":"Walczak","year":"2018","journal-title":"mBio"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.1093\/infdis\/jiac469","article-title":"Integrative genetic manipulation of Plasmodium cynomolgi reveals multidrug resistance-1 Y976F associated with increased in vitro susceptibility to mefloquine","volume":"227","author":"Ward","year":"2023","journal-title":"J. Infect. Dis."},{"key":"B51","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1146\/annurev-micro-020518-115546","article-title":"Molecular mechanisms of drug resistance in Plasmodium falciparum malaria","volume":"74","author":"Wicht","year":"2020","journal-title":"Annu. Rev. Microbiol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1186\/1475-2875-13-386","article-title":"Humanized HLA-DR4.RagKO.IL2R\u03b3cKO.NOD (DRAG) mice sustain the complex vertebrate life cycle of Plasmodium falciparum malaria","volume":"13","author":"Wijayalath","year":"2014","journal-title":"Malar. J."},{"key":"B53","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1172\/JCI11914","article-title":"Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer","volume":"107","author":"Yamamoto","year":"2001","journal-title":"J. Clin. Invest."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1111\/j.1582-4934.2008.00347.x","article-title":"Mouse models with human immunity and their application in biomedical research","volume":"13","author":"Zhang","year":"2009","journal-title":"J. Cell Mol. Med."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1453998\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T11:57:49Z","timestamp":1724155069000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1453998\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,20]]},"references-count":54,"alternative-id":["10.3389\/fmicb.2024.1453998"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1453998","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,20]]},"article-number":"1453998"}}