{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:55:11Z","timestamp":1760234111383,"version":"build-2065373602"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Apicomplexan parasites are obligatory intracellular protozoa. In the case of Toxoplasma gondii, Neospora caninum or Besnoitia besnoiti, to ensure proper tachyzoite production, they need nutrients and cell building blocks. However, apicomplexans are auxotrophic for cholesterol, which is required for membrane biosynthesis. P-glycoprotein (P-gp) is a transmembrane transporter involved in xenobiotic efflux. However, the physiological role of P-gp in cholesterol metabolism is unclear. Here, we analyzed its impact on parasite proliferation in T. gondii-, N. caninum- and B. besnoiti-infected primary endothelial cells by applying different generations of P-gp inhibitors. Host cell treatment with verapamil and valspodar significantly diminished tachyzoite production in all three parasite species, whereas tariquidar treatment affected proliferation only in B. besnoiti. 3D-holotomographic analyses illustrated impaired meront development driven by valspodar treatment being accompanied by swollen parasitophorous vacuoles in the case of T. gondii. Tachyzoite and host cell pre-treatment with valspodar affected infection rates in all parasites. Flow cytometric analyses revealed verapamil treatment to induce neutral lipid accumulation. The absence of a pronounced anti-parasitic impact of tariquidar, which represents here the most selective P-gp inhibitor, suggests that the observed effects of verapamil and valspodar are associated with mechanisms independent of P-gp. Out of the three species tested here, this compound affected only B. besnoiti proliferation and its effect was much milder as compared to verapamil and valspodar.<\/jats:p>","DOI":"10.3390\/pathogens10040395","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T14:51:12Z","timestamp":1616683872000},"page":"395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["P-Glycoprotein Inhibitors Differently Affect Toxoplasma gondii, Neospora caninum and Besnoitia besnoiti Proliferation in Bovine Primary Endothelial Cells"],"prefix":"10.3390","volume":"10","author":[{"given":"Camilo","family":"Larrazabal","sequence":"first","affiliation":[{"name":"Biomedical Research Center Seltersberg, Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-9983","authenticated-orcid":false,"given":"Liliana M. R.","family":"Silva","sequence":"additional","affiliation":[{"name":"Biomedical Research Center Seltersberg, Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Learta","family":"Pervizaj-Oruqaj","sequence":"additional","affiliation":[{"name":"The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany"},{"name":"Member of the German Center for Lung Research (DZL), Department of Pulmonary and Critical Care Medicine and Infectious Diseases, Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Herold","sequence":"additional","affiliation":[{"name":"The Cardio-Pulmonary Institute (CPI), 35392 Giessen, Germany"},{"name":"Member of the German Center for Lung Research (DZL), Department of Pulmonary and Critical Care Medicine and Infectious Diseases, Universities of Giessen and Marburg Lung Center (UGMLC), Justus-Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4550-8492","authenticated-orcid":false,"given":"Carlos","family":"Hermosilla","sequence":"additional","affiliation":[{"name":"Biomedical Research Center Seltersberg, Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Taubert","sequence":"additional","affiliation":[{"name":"Biomedical Research Center Seltersberg, Institute of Parasitology, Justus Liebig University Giessen, 35392 Giessen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Archibald, J.M., Simpson, A.G.B., and Slamovits, C.H. (2017). Apicomplexa. Handbook of the Protists, Springer International Publishing.","DOI":"10.1007\/978-3-319-28149-0"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1863-2378.2009.01276.x","article-title":"A brief history and overview of Toxoplasma gondii","volume":"57","author":"Innes","year":"2010","journal-title":"Zoonoses Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jcpa.2017.04.003","article-title":"Ovine Toxoplasmosis: A New Look at its Pathogenesis","volume":"157","author":"Benavides","year":"2017","journal-title":"J. Comp. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Nayeri, T., Sarvi, S., Moosazadeh, M., Amouei, A., Hosseininejad, Z., and Daryani, A. (2020). The global seroprevalence of anti-Toxoplasma gondii antibodies in women who had spontaneous abortion: A systematic review and meta-analysis. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008103"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"446","DOI":"10.3389\/fvets.2019.00446","article-title":"Controlling Endemic Neospora caninum-Related Abortions in a Dairy Herd From Argentina","volume":"6","author":"Lagomarsino","year":"2019","journal-title":"Front. Vet. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.ijpara.2012.10.022","article-title":"What is the global economic impact of Neospora caninum in cattle-the billion dollar question","volume":"43","author":"Reichel","year":"2013","journal-title":"Int. J. Parasitol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.pt.2013.06.002","article-title":"A century of bovine besnoitiosis: An unknown disease re-emerging in Europe","volume":"29","author":"Frey","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6650","DOI":"10.1038\/s41598-019-43153-2","article-title":"Besnoitia besnoiti infection alters both endogenous cholesterol de novo synthesis and exogenous LDL uptake in host endothelial cells","volume":"9","author":"Silva","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.vetpar.2006.07.021","article-title":"Dynamics of transcription of immunomodulatory genes in endothelial cells infected with different coccidian parasites","volume":"142","author":"Taubert","year":"2006","journal-title":"Vet. Parasitol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.vetimm.2006.03.017","article-title":"Toxoplasma gondii and Neospora caninum infections of bovine endothelial cells induce endothelial adhesion molecule gene transcription and subsequent PMN adhesion","volume":"112","author":"Taubert","year":"2006","journal-title":"Vet. Immunol. Immunopathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1007\/s00436-020-06744-x","article-title":"Besnoitia besnoiti-driven endothelial host cell cycle alteration","volume":"119","author":"Herold","year":"2020","journal-title":"Parasitol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12496","DOI":"10.1038\/s41598-019-48961-0","article-title":"Toxoplasma gondii-induced host cellular cell cycle dysregulation is linked to chromosome missegregation and cytokinesis failure in primary endothelial host cells","volume":"9","author":"Velasquez","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1128\/EC.00262-14","article-title":"Neospora caninum Recruits Host Cell Structures to Its Parasitophorous Vacuole and Salvages Lipids from Organelles","volume":"14","author":"Nolan","year":"2015","journal-title":"Eukaryot. Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1083\/jcb.149.1.167","article-title":"Toxoplasma gondii exploits host low-density lipoprotein receptor-mediated endocytosis for cholesterol acquisition","volume":"149","author":"Coppens","year":"2000","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1111\/cmi.12107","article-title":"Cryptosporidium parvum scavenges LDL-derived cholesterol and micellar cholesterol internalized into enterocytes","volume":"15","author":"Ehrenman","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1292\/jvms.10-0496","article-title":"Host cholesterol synthesis contributes to growth of intracellular Toxoplasma gondii in macrophages","volume":"73","author":"Nishikawa","year":"2011","journal-title":"J. Vet. Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1126\/science.290.5497.1721","article-title":"How cells handle cholesterol","volume":"290","author":"Simons","year":"2000","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"509","DOI":"10.3389\/fendo.2018.00509","article-title":"Sterol Metabolism and Transport in Atherosclerosis and Cancer","volume":"9","author":"Yamauchi","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1152\/ajpendo.90926.2008","article-title":"Acyl-coenzyme A:cholesterol acyltransferases","volume":"297","author":"Chang","year":"2009","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11009","DOI":"10.1074\/jbc.M116.768176","article-title":"The Coccidian Parasites Toxoplasma and Neospora Dysregulate Mammalian Lipid Droplet Biogenesis","volume":"292","author":"Hu","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/S0022-2275(20)31588-1","article-title":"The human ATP-binding cassette (ABC) transporter superfamily","volume":"42","author":"Dean","year":"2001","journal-title":"J. Lipid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1111\/j.1365-2958.2010.07169.x","article-title":"Novel roles for ATP-binding cassette G transporters in lipid redistribution in Toxoplasma","volume":"76","author":"Ehrenman","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Satyamoorthy, K., and Sharom, F.J. (2014). Complex Interplay between the P-Glycoprotein Multidrug Efflux Pump and the Membrane: Its Role in Modulating Protein Function. PLoS ONE, 4.","DOI":"10.3389\/fonc.2014.00041"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"265","DOI":"10.3389\/fonc.2020.00265","article-title":"Perplexing Role of P-Glycoprotein in Tumor Microenvironment","volume":"10","author":"Robinson","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.molbiopara.2008.09.010","article-title":"Molecular characterization and expression analysis of a P-glycoprotein homologue in Toxoplasma gondii","volume":"163","author":"Schmid","year":"2009","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1128\/AAC.00587-08","article-title":"Characterization of an ABCG-like transporter from the protozoan parasite Leishmania with a role in drug resistance and transbilayer lipid movement","volume":"52","author":"Gamarro","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/316817a0","article-title":"Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines","volume":"316","author":"Riordan","year":"1985","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kasinathan, R.S., Morgan, W.M., and Greenberg, R.M. (2011). Genetic knockdown and pharmacological inhibition of parasite multidrug resistance transporters disrupts egg production in Schistosoma mansoni. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0001425"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1017\/S0031182009990345","article-title":"P-glycoprotein interfering agents potentiate ivermectin susceptibility in ivermectin sensitive and resistant isolates of Teladorsagia circumcincta and Haemonchus contortus","volume":"136","author":"Bartley","year":"2009","journal-title":"Parasitology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.parint.2013.09.017","article-title":"P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus","volume":"63","author":"Nicolao","year":"2014","journal-title":"Parasitol. Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"17438","DOI":"10.1074\/jbc.M809420200","article-title":"Host cell P-glycoprotein is essential for cholesterol uptake and replication of Toxoplasma gondii","volume":"284","author":"Bottova","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1128\/AAC.45.1.73-78.2001","article-title":"Role of P glycoprotein in the course and treatment of Encephalitozoon microsporidiosis","volume":"45","author":"Leitch","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.2174\/092986712800167392","article-title":"Three decades of P-gp inhibitors: Skimming through several generations and scaffolds","volume":"19","author":"Palmeira","year":"2012","journal-title":"Curr. Med. Chem."},{"key":"ref_34","first-page":"1967","article-title":"Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil","volume":"41","author":"Tsuruo","year":"1981","journal-title":"Cancer Res."},{"key":"ref_35","first-page":"603","article-title":"Analysis of the interactions of SDZ PSC 833 ([3\u2019-keto-Bmt1]-Val2]-Cyclosporine), a multidrug resistance modulator, with P-glycoprotein","volume":"7","author":"Rzepka","year":"1995","journal-title":"Oncol. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1023\/A:1006046201497","article-title":"PSC-833, a frontier in modulation of P-glycoprotein mediated multidrug resistance","volume":"17","author":"Atadja","year":"1998","journal-title":"Cancer Metastasis Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/sj.bjp.0702807","article-title":"The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein","volume":"128","author":"Martin","year":"1999","journal-title":"Br. J. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0960-894X(99)00030-X","article-title":"Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives","volume":"9","author":"Roe","year":"1999","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/nrmicro3139","article-title":"Targeting lipid biosynthesis and salvage in apicomplexan parasites for improved chemotherapies","volume":"11","author":"Coppens","year":"2013","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Bottova, I., Sauder, U., Olivieri, V., Hehl, A.B., and Sonda, S. (2010). The P-glycoprotein inhibitor GF120918 modulates Ca2+-dependent processes and lipid metabolism in Toxoplasma gondii. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0010062"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1128\/AAC.38.6.1392","article-title":"In vitro effects of artemisinin ether, cycloguanil hydrochloride (alone and in combination with sulfadiazine), quinine sulfate, mefloquine, primaquine phosphate, trifluoperazine hydrochloride, and verapamil on Toxoplasma gondii","volume":"38","author":"Holfels","year":"1994","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0006-2952(97)00482-6","article-title":"Synergy between two calcium channel blockers, verapamil and fantofarone (SR33557), in reversing chloroquine resistance in Plasmodium falciparum","volume":"55","author":"Adovelande","year":"1998","journal-title":"Biochem. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"22393","DOI":"10.1074\/jbc.270.38.22393","article-title":"Verapamil reversal of chloroquine resistance in the malaria parasite Plasmodium falciparum is specific for resistant parasites and independent of the weak base effect","volume":"270","author":"Martiney","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/0021-9150(86)90002-X","article-title":"Primary culture of human aortic intima cells as a model for testing antiatherosclerotic drugs. Effects of cyclic AMP, prostaglandins, calcium antagonists, antioxidants, and lipid-lowering agents","volume":"60","author":"Orekhov","year":"1986","journal-title":"Atherosclerosis"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0014-4800(86)90044-4","article-title":"Effect of calcium on cell proliferation and extracellular matrix synthesis in arterial smooth muscle cells and dermal fibroblasts","volume":"44","author":"Rokosova","year":"1986","journal-title":"Exp. Mol. Pathol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1161\/01.ATV.7.6.585","article-title":"Long-term effects of verapamil on aortic smooth muscle cells cultured in the presence of hypercholesterolemic serum","volume":"7","author":"Stein","year":"1987","journal-title":"Arteriosclerosis"},{"key":"ref_47","first-page":"462","article-title":"L-651,582 inhibition of intracellular parasitic protozoal growth correlates with host-cell directed effects","volume":"256","author":"Hupe","year":"1991","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_48","unstructured":"Polin, R.A., Fox, W.W., and Abman, S.H. (2004). Fetal and Neonatal Physiology, W.B. Saunders Co.. [3rd ed.]."},{"key":"ref_49","first-page":"100","article-title":"Verapamil inhibits the glucose transport activity of GLUT1","volume":"6","author":"Louters","year":"2010","journal-title":"J. Med. Toxicol. Off. J. Am. Coll. Med Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1128\/AAC.41.9.1859","article-title":"Characterization of anti-Toxoplasma activity of SDZ 215-918, a cyclosporin derivative lacking immunosuppressive and peptidyl-prolyl-isomerase-inhibiting activity: Possible role of a P glycoprotein in Toxoplasma physiology","volume":"41","author":"Silverman","year":"1997","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0006-2952(94)90279-8","article-title":"Roles of peptidyl-prolyl cis-trans isomerase and calcineurin in the mechanisms of antimalarial action of cyclosporin A, FK506, and rapamycin","volume":"48","author":"Bell","year":"1994","journal-title":"Biochem. Pharmacol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1128\/AAC.42.4.843","article-title":"Cyclosporin analogs inhibit in vitro growth of Cryptosporidium parvum","volume":"42","author":"Perkins","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1128\/MMBR.64.3.607-623.2000","article-title":"Lytic cycle of Toxoplasma gondii","volume":"64","author":"Black","year":"2000","journal-title":"Microbiol. Mol. Biol. Rev. MMBR"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1574-6968.2009.01799.x","article-title":"Dynamin inhibitor impairs Toxoplasma gondii invasion","volume":"301","author":"Caldas","year":"2009","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1194\/jlr.M500255-JLR200","article-title":"Reevaluation of the role of the multidrug-resistant P-glycoprotein in cellular cholesterol homeostasis","volume":"47","author":"Settle","year":"2006","journal-title":"J. Lipid Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.bbalip.2012.11.002","article-title":"Cyclosporine A and PSC833 inhibit ABCA1 function via direct binding","volume":"1831","author":"Nagao","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1161\/01.ATV.0000117178.94087.ba","article-title":"Verapamil increases the apolipoprotein-mediated release of cellular cholesterol by induction of ABCA1 expression via Liver X receptor-independent mechanism","volume":"24","author":"Suzuki","year":"2004","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_58","first-page":"39","article-title":"Protective effects of verapamil against isoprenaline- induced mobilization of mitochondrial calcium and cellular lipid droplets in the myocardium","volume":"181","author":"Saetersdal","year":"1982","journal-title":"Res. Exp. Med. Z. Fur Die Gesamte Exp. Med. Einschl. Exp. Chir."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.1007\/s00436-014-4094-3","article-title":"Besnoitia besnoiti tachyzoites induce monocyte extracellular trap formation","volume":"113","author":"Silva","year":"2014","journal-title":"Parasitol. Res."},{"key":"ref_60","first-page":"333","article-title":"Antiparasitic Efficacy of Curcumin Against Besnoitia besnoiti Tachyzoites in vitro","volume":"5","author":"Hermosilla","year":"2018","journal-title":"Front. Vet. Sci."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/4\/395\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:41:11Z","timestamp":1760161271000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/4\/395"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["pathogens10040395"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10040395","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2021,3,25]]}}}