{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:04:35Z","timestamp":1789016675321,"version":"build-2803163510"},"reference-count":89,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2021,3,24]],"date-time":"2021-03-24T00:00:00Z","timestamp":1616544000000},"content-version":"am","delay-in-days":352,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["POS_FMV_2015_1_1005183"],"award-info":[{"award-number":["POS_FMV_2015_1_1005183"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006049","name":"Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica","doi-asserted-by":"publisher","award":["grant CSIC_POS_362"],"award-info":[{"award-number":["grant CSIC_POS_362"]}],"id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008725","name":"Agencia Nacional de Investigaci\u00f3n e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["POS_FMV_2015_1_1005183"],"award-info":[{"award-number":["POS_FMV_2015_1_1005183"]}],"id":[{"id":"10.13039\/100008725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006049","name":"Comisi\u00f3n Sectorial de Investigaci\u00f3n Cient\u00edfica","doi-asserted-by":"crossref","award":["grant CSIC_POS_362"],"award-info":[{"award-number":["grant CSIC_POS_362"]}],"id":[{"id":"10.13039\/501100006049","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>There is an urgent need to develop new drugs against Chagas\u2019 disease. In addition, the mechanisms of action of existing drugs have not been completely worked out at the molecular level. High throughput approaches have been demonstrated to be powerful tools not only for understanding the basic biology of Trypanosoma cruzi, but also for the identification of drug targets such as proteins or pathways that are essential for parasite infection and survival within the mammalian host. Here, we have applied these tools towards the discovery of the effects of two organometallic compounds with trypanocidal activity, Pd\u2013dppf\u2013mpo and Pt\u2013dppf\u2013mpo, on the transcriptome and proteome of T. cruzi epimastigotes. These approaches have not yet been reported for any other prospective metal-based anti T. cruzi drug. We found differentially expressed transcripts and proteins in treated parasites. Pd\u2013dppf\u2013mpo treatment resulted in more modulated transcripts (2327 of 10\u2009785 identified transcripts) than Pt\u2013dppf\u2013mpo treatment (201 of 10\u2009773 identified transcripts) suggesting a mechanism of action for Pd\u2013dppf\u2013mpo at the transcriptome level. Similar numbers of differentially expressed proteins (342 and 411 for Pd\u2013dppf\u2013mpo and Pt\u2013dppf\u2013mpo respectively) were also observed. We further functionally categorized differentially expressed transcripts and identified cellular processes and pathways significantly impacted by treatment with the compounds. Transcripts involved in DNA binding, protein metabolism, transmembrane transport, oxidative defense, and the ergosterol pathways were found to be modulated by the presence of the compounds. Our transcriptomic dataset also contained previously validated essential genes. These data allowed us to hypothesize a multimodal mechanism of action for the trypanocidal activity of Pd\u2013dppf\u2013mpo and Pt\u2013dppf\u2013mpo, and a differential contribution of the metal moiety of each compound.<\/jats:p>","DOI":"10.1039\/d0mt00030b","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T16:26:07Z","timestamp":1585067167000},"page":"813-828","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comparative high-throughput analysis of the <i>Trypanosoma cruzi<\/i> response to organometallic compounds"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0536-591X","authenticated-orcid":false,"given":"M Florencia","family":"Mosquillo","sequence":"first","affiliation":[{"name":"Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo, Uruguay. Fax: +598-25258617; Tel: +598-25258618"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3856-3920","authenticated-orcid":false,"given":"Pablo","family":"Smircich","sequence":"additional","affiliation":[{"name":"Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo, Uruguay. Fax: +598-25258617; Tel: +598-25258618"},{"name":"Instituto de Investigaciones Biol\u00f3gicas Clemente Estable, Montevideo, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3229-3365","authenticated-orcid":false,"given":"Mart\u00edn","family":"Ciganda","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University at Buffalo, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1855-2327","authenticated-orcid":false,"given":"Anal\u00eda","family":"Lima","sequence":"additional","affiliation":[{"name":"Instituto de Investigaciones Biol\u00f3gicas Clemente Estable, Montevideo, Uruguay"},{"name":"Unidad de Bioqu\u00edmica y Prote\u00f3mica Anal\u00edticas, Institut Pasteur de Montevideo, Montevideo, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8678-7374","authenticated-orcid":false,"given":"Dinorah","family":"Gambino","sequence":"additional","affiliation":[{"name":"\u00c1rea Qu\u00edmica Inorg\u00e1nica, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica, Montevideo, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-8244","authenticated-orcid":false,"given":"Beatriz","family":"Garat","sequence":"additional","affiliation":[{"name":"Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo, Uruguay. Fax: +598-25258617; Tel: +598-25258618"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5084-7619","authenticated-orcid":false,"given":"Leticia","family":"P\u00e9rez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Laboratorio de Interacciones Moleculares, Facultad de Ciencias, Universidad de la Rep\u00fablica, Montevideo, Uruguay. Fax: +598-25258617; Tel: +598-25258618"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"2021121004463028500_cit1","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1053\/j.semdp.2019.04.008","article-title":"Chagas disease as example of a reemerging parasite","volume":"36","author":"Guarner","year":"2019","journal-title":"Semin. Diagn. 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Dis."},{"key":"2021121004463028500_cit4","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3201\/eid2501.180646","article-title":"Oral Transmission of Trypanosoma cruzi, Brazilian Amazon","volume":"25","author":"Santana","year":"2019","journal-title":"Emerging Infect. Dis."},{"key":"2021121004463028500_cit5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exppara.2015.12.017","article-title":"Sexual transmission of Trypanosoma cruzi in murine model","volume":"162","author":"Ribeiro","year":"2016","journal-title":"Exp. Parasitol."},{"key":"2021121004463028500_cit6","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.2174\/0929867323999160625124424","article-title":"Challenges in Chagas Disease Drug Discovery: A Review","volume":"23","author":"Paucar","year":"2016","journal-title":"Curr. Med. 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