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ABC transporter and benznidazole resistance in Trypanosoma cruzi; production of the phytohormone indole acetic acid (IAA) in Phytomonas serpens

Grant number: 10/50957-1
Support Opportunities:Regular Research Grants
Duration: August 01, 2010 - December 31, 2012
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Bianca Silvana Zingales
Grantee:Bianca Silvana Zingales
Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil


This proposal is constituted by two subprojects that represent the continuation of studies supported by FAPESP. In subproject 1 we aim at investigating the involvement of a ABC transporter in the natural resistance of Trypanosoma cruzi isolates to benznidazole (BZ). BZ is one of the two drugs used in the treatment of Chagas disease. Geographic differences in the therapeutic outcome have been attributed to variations in BZ susceptibility of infecting strains. Previous evidence obtained by our group based on the differential hybridization in DNA microarrays and real time RT-PCR suggests that a T. cruzi ABC transporter of the G subfamily, named TcABCG1, participates in the process. The goals of subproject 1 are: (i) to clone and sequence the TcABCG1 gene of BZ susceptible and resistant strains; to verify the presence of SNPs and determine the number of gene copies; (ii) to verify the action of ABC transporter inhibitors in the decrease of BZ resistance; (iii) to verify whether the superexpression of TcABCG1 gene enhances resistance to BZ and nifurtimox. The major goal of subproject 2 is to investigate the production of the phytohormone indole acetic acid (IAA) in Phytomonas serpens and its functionality. In this plant protozoan we have characterized a gene that shows high similarity to indolepiruvate decarboxylases (IPDCs) of bacteria and with putative piruvate/IPDCs of Leishmania species. Interestingly the gene has no ortologues in T. cruzi and T. brucei. IPDC is in the biosynthetic pathway of IAA, one of the most important plant hormones. We intend to characterize the presence of IAA in the conditioned culture media of P. serpens and L. major, and determine some kinetic parameters of the enzymatic reaction in the two organisms and in the recombinant protein TcABCG1. Finally, we intend to investigate the functionality of the phytohormone produced by P. serpens in classical plant physiology assays. (AU)

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Scientific publications
(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)
IENNE, SUSAN; FRESCHI, LUCIANO; VIDOTTO, VANESSA F.; DE SOUZA, TIAGO A.; PURGATTO, EDUARDO; ZINGALES, BIANCA. Auxin production by the plant trypanosomatid Phytomonas serpens and auxin homoeostasis in infected tomato fruits. Parasitology, v. 141, n. 10, p. 1299-1310, . (10/50957-1)

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