Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33711 http://dx.doi.org/10.1371/journal.pone.0019733 |
Resumo: | The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. the screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. the 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. in addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy. |
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Genovesio, AugusteGiardini, Miriam A.Kwon, Yong-JunDossin, Fernando de MacedoChoi, Seo YeonKim, Nam YoulKim, Hi ChulJung, Sung YongSchenkman, Sergio [UNIFESP]Almeida, Igor C.Emans, NeilFreitas-Junior, Lucio H.Inst Pasteur KoreaYonsei UnivUniversidade Federal de São Paulo (UNIFESP)Univ Texas El PasoCSIR Biosci2016-01-24T14:16:46Z2016-01-24T14:16:46Z2011-05-20Plos One. San Francisco: Public Library Science, v. 6, n. 5, 13 p., 2011.1932-6203http://repositorio.unifesp.br/handle/11600/33711http://dx.doi.org/10.1371/journal.pone.0019733WOS000290793400009.pdf10.1371/journal.pone.0019733WOS:000290793400009The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. the screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. the 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. in addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy.Korean Government (MEST)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)NIHInst Pasteur Korea, Image Min Grp, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Ctr Neglected Dis Drug Discovery, Songnam, Gyeonggi Do, South KoreaInst Pasteur Korea, Discovery Biol Grp, Songnam, Gyeonggi Do, South KoreaYonsei Univ, Dept Biochem, Seoul 120749, South KoreaYonsei Univ, Natl Res Lab, Seoul 120749, South KoreaUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilUniv Texas El Paso, Dept Biol Sci, Border Biomed Res Ctr, El Paso, TX 79968 USACSIR Biosci, Synthet Biol ERA, High Throughput Biol Grp, Pretoria, South AfricaUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilKorean Government (MEST): K204EA000001-09E0100-00110NIH: 2S06GM00812NIH: 1R01AI070655NIH: 5G12RR008124-16A1Web of Science13engPublic Library SciencePlos OneVisual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000290793400009.pdfapplication/pdf3187890${dspace.ui.url}/bitstream/11600/33711/1/WOS000290793400009.pdf3f70ca92bd4407b73cb06cb25b6ac050MD51open accessTEXTWOS000290793400009.pdf.txtWOS000290793400009.pdf.txtExtracted texttext/plain71154${dspace.ui.url}/bitstream/11600/33711/2/WOS000290793400009.pdf.txt38e4c253551da9387712261e5636808fMD52open access11600/337112023-01-12 21:39:41.998open accessoai:repositorio.unifesp.br:11600/33711Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:10:06.357336Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection |
title |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection |
spellingShingle |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection Genovesio, Auguste |
title_short |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection |
title_full |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection |
title_fullStr |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection |
title_full_unstemmed |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection |
title_sort |
Visual Genome-Wide RNAi Screening to Identify Human Host Factors Required for Trypanosoma cruzi Infection |
author |
Genovesio, Auguste |
author_facet |
Genovesio, Auguste Giardini, Miriam A. Kwon, Yong-Jun Dossin, Fernando de Macedo Choi, Seo Yeon Kim, Nam Youl Kim, Hi Chul Jung, Sung Yong Schenkman, Sergio [UNIFESP] Almeida, Igor C. Emans, Neil Freitas-Junior, Lucio H. |
author_role |
author |
author2 |
Giardini, Miriam A. Kwon, Yong-Jun Dossin, Fernando de Macedo Choi, Seo Yeon Kim, Nam Youl Kim, Hi Chul Jung, Sung Yong Schenkman, Sergio [UNIFESP] Almeida, Igor C. Emans, Neil Freitas-Junior, Lucio H. |
author2_role |
author author author author author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Inst Pasteur Korea Yonsei Univ Universidade Federal de São Paulo (UNIFESP) Univ Texas El Paso CSIR Biosci |
dc.contributor.author.fl_str_mv |
Genovesio, Auguste Giardini, Miriam A. Kwon, Yong-Jun Dossin, Fernando de Macedo Choi, Seo Yeon Kim, Nam Youl Kim, Hi Chul Jung, Sung Yong Schenkman, Sergio [UNIFESP] Almeida, Igor C. Emans, Neil Freitas-Junior, Lucio H. |
description |
The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical infection that affects millions of people in the Americas. Current chemotherapy relies on only two drugs that have limited efficacy and considerable side effects. Therefore, the development of new and more effective drugs is of paramount importance. Although some host cellular factors that play a role in T. cruzi infection have been uncovered, the molecular requirements for intracellular parasite growth and persistence are still not well understood. To further study these host-parasite interactions and identify human host factors required for T. cruzi infection, we performed a genome-wide RNAi screen using cellular microarrays of a printed siRNA library that spanned the whole human genome. the screening was reproduced 6 times and a customized algorithm was used to select as hits those genes whose silencing visually impaired parasite infection. the 162 strongest hits were subjected to a secondary screening and subsequently validated in two different cell lines. Among the fourteen hits confirmed, we recognized some cellular membrane proteins that might function as cell receptors for parasite entry and others that may be related to calcium release triggered by parasites during cell invasion. in addition, two of the hits are related to the TGF-beta signaling pathway, whose inhibition is already known to diminish levels of T. cruzi infection. This study represents a significant step toward unveiling the key molecular requirements for host cell invasion and revealing new potential targets for antiparasitic therapy. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-05-20 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:16:46Z |
dc.date.available.fl_str_mv |
2016-01-24T14:16:46Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Plos One. San Francisco: Public Library Science, v. 6, n. 5, 13 p., 2011. |
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http://repositorio.unifesp.br/handle/11600/33711 http://dx.doi.org/10.1371/journal.pone.0019733 |
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1932-6203 |
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WOS000290793400009.pdf |
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10.1371/journal.pone.0019733 |
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Plos One. San Francisco: Public Library Science, v. 6, n. 5, 13 p., 2011. 1932-6203 WOS000290793400009.pdf 10.1371/journal.pone.0019733 WOS:000290793400009 |
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http://repositorio.unifesp.br/handle/11600/33711 http://dx.doi.org/10.1371/journal.pone.0019733 |
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