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Host-parasite interaction: models for studying virulence and tropism


We propose to study factors involved in the attenuation and tropism of Leishmania parasites. The proposal is composed by two projects. We will investigate what happens in the interaction with the host of a Leishmania major mutant overexpressing the Spliced Leader RNA (SL RNA) regarding mechanisms involved in the immunomodulatory action of the mutant. We will explore the potential of this mutant to generate a live vaccine. The SL RNA mutant has been generated and characterized in the laboratory and we have already proven the correlation between virulence attenuation in vivo and the presence of the ectopic SLRNA. It is relevant to characterize characterize the immune response profile of animal-models with different genetic background to further explore the mutant as the starting point for the generation of a live vaccine. The second project aims to investigate one factor potentially associated with tropism and infectivity of L. braziliensis. We will use clinical isolates obtained from cutaneous and mucosal lesions from a single individual (4 isolates from two patients), which have already been shown to present differential patterns of gene expression. Prostaglandin F2 alpha synthase (PFGS) was found to be consistently augmented in both cutaneous isolates and the protein has also been associated with an increased level of infectivity in the site of inoculation. In addition, the protein is considered a potential target for novel drugs against leishmaniasis ( Our proposal is to genetically validate the relevance of PFGS for the survival and infection profile in vivo and in vitro. For that we will generate and characterize two Leishmania transfectants; one overexpressing PFGS and a PGFS knockout mutant. The protein has also been expressed in E. coli and purified for antigen generation, which will be useful for determining its localization within or outside the cell. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARNEIRO ALVES-FERREIRA, ELIZA VANESSA; FERREIRA, TIAGO RODRIGUES; WALRAD, PEGINE; KAYE, PAUL M.; CRUZ, ANGELA KAYSEL. Leishmania braziliensis prostaglandin F-2 alpha synthase impacts host infection. PARASITES & VECTORS, v. 13, n. 1 JAN 8 2020. Web of Science Citations: 0.
GARCIA, JULIANA B. F.; VIEIRA DA ROCHA, JOAO P.; COSTA-SILVA, HELLIDA M.; ALVES, CERES L.; MACHADO, CARLOS R.; CRUZ, ANGELA K. Leishmania major and Trypanosoma cruzi present distinct DNA damage responses. Molecular and Biochemical Parasitology, v. 207, n. 1, p. 23-32, MAY 2016. Web of Science Citations: 2.
ALVES-FERREIRA, ELIZA V. C.; TOLEDO, JULIANO S.; DE OLIVEIRA, ARTHUR H. C.; FERREIRA, TIAGO R.; RUY, PATRICIA C.; PINZAN, CAMILA F.; SANTOS, RAMON F.; BOAVENTURA, VIVIANE; ROJO, DAVID; LOPEZ-GONZALVEZ, ANGELEZ; ROSA, JOSE C.; BARBAS, CORAL; BARRAL-NETTO, MANOEL; BARRAL, ALDINA; CRUZ, ANGELA K. Differential Gene Expression and Infection Profiles of Cutaneous and Mucosal Leishmania braziliensis Isolates from the Same Patient. PLoS Neglected Tropical Diseases, v. 9, n. 9 SEP 2015. Web of Science Citations: 16.
FERREIRA, TIAGO R.; ALVES-FERREIRA, ELIZA V. C.; DEFINA, TANIA P. A.; WALRAD, PEGINE; PAPADOPOULOU, BARBARA; CRUZ, ANGELA K. Altered expression of an RBP-associated arginine methyltransferase 7 in Leishmania major affects parasite infection. Molecular Microbiology, v. 94, n. 5, p. 1085-1102, DEC 2014. Web of Science Citations: 12.

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