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dc.contributor.author
Perez Brandan, Cecilia Maria
dc.contributor.author
Padilla, Ángel M.
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Xu, Dan
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Tarleton, Rick L.
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Basombrio, Miguel Angel Manuel
dc.date.available
2017-05-10T21:21:30Z
dc.date.issued
2011-12-13
dc.identifier.citation
Perez Brandan, Cecilia Maria; Padilla, Ángel M.; Xu, Dan; Tarleton, Rick L.; Basombrio, Miguel Angel Manuel; Knockout of the dhfr-ts Gene in Trypanosoma cruzi Generates Attenuated Parasites Able to Confer Protection Against a Virulent Challenge; Public Library Of Science; Neglected Tropical Diseases; 5; 12; 13-12-2011; 1-10;e1418
dc.identifier.issn
1935-2735
dc.identifier.uri
http://hdl.handle.net/11336/16250
dc.description.abstract
Background: Trypanosoma cruzi is a protozoan parasite that causes severe disease in millions of habitants of developing countries. Currently there is no vaccine to prevent this disease and the available drugs have the consequences of side effects. Live vaccines are likely to be more effective in inducing protection than recombinant proteins or DNA vaccines; however, safety problems associated to their use have been pointed out. In recent years, increasing knowledge on the molecular genetics of Trypanosomes has allowed the identification and elimination of genes that may be necessary for parasite infectivity and survival. In this sense, targeted deletion or disruption of specific genes in the parasite genome may protect against such reversion to virulent genotypes. Methods and Findings: By targeted gene disruption we generated monoallelic mutant parasites for the dhfr-ts gene in a T. cruzi strain that has been shown to be naturally attenuated. In comparison to T. cruzi wild type epimastigotes, impairment in growth of dhfr-ts+/2 mutant parasites was observed and mutant clones displayed decreased virulence in mice. Also, a lower number of T. cruzi-specific CD8+ T cells, in comparison to those induced by wild type parasites, was detected in mice infected with mutant parasites. However, no remarkable differences in the protective effect of TCC wild type versus TCC mutant parasites were observed. Mice challenged with virulent parasites a year after the original infection with the mutant parasites still displayed a significant control over the secondary infection. Conclusion: This study indicates that it is possible to generate genetically attenuated T. cruzi parasites able to confer protection against further T. cruzi infections.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library Of Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Trypanosoma Cruzi
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Dhfr-Ts
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Vaccines
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Enfermedades Infecciosas
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Knockout of the dhfr-ts Gene in Trypanosoma cruzi Generates Attenuated Parasites Able to Confer Protection Against a Virulent Challenge
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-05-02T18:16:28Z
dc.journal.volume
5
dc.journal.number
12
dc.journal.pagination
1-10;e1418
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Perez Brandan, Cecilia Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
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Fil: Padilla, Ángel M.. University of Georgia. Center for Tropical and Emerging Global Diseases; Estados Unidos
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Fil: Xu, Dan. University of Georgia. Center for Tropical and Emerging Global Diseases; Estados Unidos
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Fil: Tarleton, Rick L.. University of Georgia. Center for Tropical and Emerging Global Diseases; Estados Unidos
dc.description.fil
Fil: Basombrio, Miguel Angel Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Cs.de la Salud. Instituto de Patología Experimental; Argentina
dc.journal.title
Neglected Tropical Diseases
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pntd.0001418
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0001418