{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:59:41Z","timestamp":1791331181041,"version":"4.3.1"},"reference-count":82,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009082","name":"Universidad Cat\u00f3lica de C\u00f3rdoba","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009082","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008056","name":"Fundaci\u00f3n Florencio Fiorini","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008056","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Giardia lamblia<\/jats:italic>, a eukaryotic intestinal parasite, produces small extracellular vesicles (sEVs) as a conserved evolutionary mechanism. This study investigates the functional role of sEVs in modulating drug response traits among <jats:italic>G. lamblia<\/jats:italic> parasites. Here, we showed that sEVs derived from metronidazole (MTZ)\u2013resistant clones modify the expression of enzymes involved in MTZ metabolism and the production of reactive oxygen species (ROS) in recipient wild type parasites. The transfer efficiency and phenotypic impact vary depending on the genetic background of the isolates, highlighting a genotype\u2010specific mechanism. Our findings reveal that sEVs act as mediators of phenotypic adaptation in <jats:italic>G. lamblia<\/jats:italic>, enhancing parasite survival under drug\u2010induced stress. This study highlights the significance of sEVs in drug\u2010sensitive dynamics and lays the groundwork for investigating therapeutic interventions that target EV\u2010mediated sensitivity in giardiasis.<\/jats:p>","DOI":"10.1002\/jev2.70139","type":"journal-article","created":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T07:35:19Z","timestamp":1756712119000},"source":"Crossref","is-referenced-by-count":2,"title":["Genotype\u2010Specific Small EVs Released by <i>Giardia lamblia<\/i> Act as Mediators of Phenotypic Adaptation Under Metronidazole\u2010Induced Stress"],"prefix":"10.1002","volume":"14","author":[{"given":"Gabriel Luna","family":"Pizarro","sequence":"first","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8971-9684","authenticated-orcid":false,"given":"Jer\u00f3nimo","family":"Laiolo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"},{"name":"Universidad Cat\u00f3lica de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nehu\u00e9n","family":"Salas","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roc\u00edo G.","family":"Patolsky","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano D\u00edaz","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilo","family":"Cotelo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constanza","family":"Feliziani","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea Silvana","family":"R\u00f3polo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-6896","authenticated-orcid":false,"given":"Mar\u00eda Carolina","family":"Touz","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n M\u00e9dica Mercedes y Mart\u00edn Ferreyra, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (INIMEC\u2010CONICET) Universidad Nacional de C\u00f3rdoba  C\u00f3rdoba Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00024-19"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.40.2.446-452.2002"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000074540"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2015.04.009"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2009.05.015"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apar.2019.11.003"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40475-021-00248-z"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.07.003"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1484805"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3380"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.34"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2017.12.001"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2017.05.028"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101512-122326"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg150"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-03189-z"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111121"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giy003"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.2001.280.1.G1"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.3.1478"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.8.12.1885"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2017.01.005"},{"key":"e_1_2_11_24_1","first-page":"79","article-title":"The Molecular Pathogenesis of Giardiasis","volume":"24","author":"Farthing M. J.","year":"1997","journal-title":"Journal of Pediatric Gastroenterology and Nutrition"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-010-0073-2"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000560"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S36111"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1523880"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.114-128.2001"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2007.07.016"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fuy042"},{"key":"e_1_2_11_32_1","first-page":"155","article-title":"Giardia lamblia: The Roles of Temperature, pH, and Nutrients in Encystation and Excystation In Vitro","volume":"69","author":"Gillin F. D.","year":"1989","journal-title":"Experimental Parasitology"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1360"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1086\/498169"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2006.09.008"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7519(01)00183-7"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.2307\/3284315"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15756"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2007.12.002"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.1.6.13608"},{"key":"e_1_2_11_41_1","first-page":"543","article-title":"Genome Analysis and Comparative Genomics of a Giardia intestinalis Assemblage E Isolate","volume":"11","author":"Jerlstrom\u2010Hultqvist J.","year":"2010","journal-title":"BMC Genomics [Electronic Resource]"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(83)90120-7"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.834008"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S141468"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1645\/GE-293R"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40475-015-0051-1"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkr192"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2016.07.003"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.2003.02008.x"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.78321"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0006120"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12727"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2013.04.009"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v3.25040"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00433"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1143837"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121600"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn142"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2015.03.001"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt106"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkm205"},{"key":"e_1_2_11_62_1","first-page":"10","article-title":"Mechanisms of Antibiotic Resistance","volume":"2","author":"Munita J. M.","year":"2016","journal-title":"Microbiology Spectrum"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2018.07.003"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119559"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00044-09"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11020136"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2014.01.007"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01056-1"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/1469-0691.12327"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S177997"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10096-007-0404-3"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.7.1533"},{"key":"e_1_2_11_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-13-256"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.11.051"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00384-11"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology10050388"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182000076629"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0031182003004505"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-7646(98)80035-6"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-014-0396-y"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.12404"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12501"}],"container-title":["Journal of Extracellular Vesicles"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jev2.70139","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T17:21:34Z","timestamp":1760635294000},"score":1,"resource":{"primary":{"URL":"https:\/\/isevjournals.onlinelibrary.wiley.com\/doi\/10.1002\/jev2.70139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":82,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/jev2.70139"],"URL":"https:\/\/doi.org\/10.1002\/jev2.70139","archive":["Portico"],"relation":{},"ISSN":["2001-3078","2001-3078"],"issn-type":[{"value":"2001-3078","type":"print"},{"value":"2001-3078","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"article-number":"e70139"}}