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ThrRS intein of species from the genus Candida: phylogeny, potential molecular marker and therapeutic target

Grant number: 12/07741-3
Support Opportunities:Regular Research Grants
Duration: October 01, 2012 - May 31, 2015
Field of knowledge:Biological Sciences - Microbiology
Principal Investigator:Eduardo Bagagli
Grantee:Eduardo Bagagli
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Inteins or internal proteins are known as parasitic genetic elements, because they use the cellular machinery to keep and in some cases spread in the population. They are coding sequences that have been found in important and conserved proteins. These parasitic genetic elements are transcribed and translated with flanking sequences (exteins). After translation, the inteins are excised by an autocatalytic process and the host protein assumes its normal conformation and develops its expected function. The ThrRS intein occurs in the gene ThrRS of Candida tropicalis and in the psilosis complex, which includes C. parapsilosis, C. orthopsilosis and C. metapsilosis, the last two inteins were described previously (FAPESP 2010/02674-0). Since the protein ThrRS is vital for the cell, the ThrRS intein is considered an important therapeutic target for evaluation of drugs that may inhibit their splicing and thus prevent the function of ThrRS and cell survival. This project aims to study the functionality of the intein ThrRS deduced by the degree of conservation of motifs concerning splicing and HE, the phylogeny of the intein ThrRS in the psilosis complex, as well as to explore the therapeutic potential of this intein by evaluating its splicing activity in the plasmid pMST from a non-native protein in an E. coli model. Once the system is working, the cisplatin, which is known to inhibit the splicing of the RecA intein of Mycobacterium tuberculosis, will be tested in different concentrations, in order to evaluated whether it also interfers in the splicing of the ThrRS intein. Therefore, the study of ThrRS intein allows new therapies and diagnostics, as well as a greater understanding of molecular and phylogenetic profiles of the yeasts that have this intein. (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)
FERNANDES, JOSE A. L.; PRANDINI, TAMARA H. R.; CASTRO, MARIA DA CONCEICAO A.; ARANTES, THALES D.; GIACOBINO, JULIANA; BAGAGLI, EDUARDO; THEODORO, RAQUEL C.. Evolution and Application of Inteins in Candida species: A Review. FRONTIERS IN MICROBIOLOGY, v. 7, . (12/07741-3, 12/04003-1)
ROCHA PRANDINI, TAMARA HELOISA; THEODORO, RAQUEL CORDEIRO; BRUDER-NASCIMENTO, ARIANE C. M. O.; SCHEEL, CHRISTINA M.; BAGAGLI, EDUARDO. Analysis of Inteins in the Candida parapsilosis Complex for Simple and Accurate Species Identification. Journal of Clinical Microbiology, v. 51, n. 9, p. 2830-2836, . (12/07741-3, 12/04003-1)
GIACOBINO, JULIANA; MONTELLI, AUGUSTO CEZAR; BARRETTI, PASQUAL; BRUDER-NASCIMENTO, ARIANE; CARAMORI, JACQUELINE TEIXEIRA; BARBOSA, LUCIANO; BAGAGLI, EDUARDO. Fungal peritonitis in patients undergoing peritoneal dialysis (PD) in Brazil: molecular identification, biofilm production and antifungal susceptibility of the agents. Medical Mycology, v. 54, n. 7, p. 725-732, . (12/07741-3, 11/03836-7)

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