PRP8 intein in pathogenic fungi: evolutionary aspects and therapeutic potential

• Grant number: 10/08839-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2010
• End date: February 28, 2013
• Field of knowledge: Biological Sciences - Microbiology
• Principal Investigator: Eduardo Bagagli
• Grantee: Raquel Cordeiro Theodoro
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Inteins are intervening coding sequences which are transcribed and translated together with their host genes and then perform an autocatalytic protein splicing, allowing the host protein to assume its functional conformation. The PRP8 intein occurs in the PRP8 gene in a significant number of fungal species, including the pathogens from genera Paracoccidoides, Blastomyces, Histoplasma, Emmonsia, Aspergillus and Cryptococcus. Due to the importance of the Prp8 protein, the PRP8 intein is considered an important therapeutic target for the evaluation of drugs that might inhibit its splicing, and consequently the correct expression of the Prp8 protein, avoiding therefore, the proliferation of fungal cell. This project aim to describe and phylogenetic analyze the PRP8 intein in pathogenic species from Onygenales order and also to create an in vivo system, in Saccharomyces cerevisiae, for the evaluation of drugs on the functionality of the PRP8 intein. The zinc will be tested as possible positive control, since it has already been shown to inhibit the splicing of the RecA and DnaE inteins. Once functional, this system can be usefull for the evaluation of potentially antifungal substances, such as plant extracts/oils in collaboration with other research groups. This is a new approach that will be introduced in the lab of Fungal Biology at the Dept of Microbiologya and Immunology from this Instituto, couting with the national and international collaboration of experts in this fiel.

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)

THEODORO, RAQUEL CORDEIRO; SCHEEL, CHRISTINA M.; BRANDT, MARY E.; KASUGA, TAKAO; BAGAGLI, EDUARDO. PRP8 intein in cryptic species of Histoplasma capsulatum: Evolution and phylogeny. INFECTION GENETICS AND EVOLUTION, v. 18, p. 174-182, AUG 2013. (10/08839-1)

FERNANDES, JOSE ALEX LOURENCO; ZATTI, MATHEUS DA SILVA; ARANTES, THALES DOMINGOS; DE SOUZA, MARIA FERNANDA BEZERRA; SANTONI, MARIANA MARCHI; ROSSI, DANUZA; ZANELLI, CLESLEI FERNANDO; LIU, XIANG-QIN; BAGAGLI, EDUARDO; THEODORO, RAQUEL CORDEIRO. Cryptococcus neoformans Prp8 Intein: An In Vivo Target-Based Drug Screening System in Saccharomyces cerevisiae to Identify Protein Splicing Inhibitors and Explore Its Dynamics. JOURNAL OF FUNGI, v. 8, n. 8, p. 15-pg., 2022-08-01. (10/08839-1)

THEODORO, RAQUEL CORDEIRO; TEIXEIRA, MARCUS DE MELO; SOARES FELIPE, MARIA SUELI; DOS SANTOS PADUAN, KARINA; RIBOLLA, PAULO MARTINS; SAN-BLAS, GIOCONDA; BAGAGLI, EDUARDO. Genus Paracoccidioides: Species Recognition and Biogeographic Aspects. PLoS One, v. 7, n. 5, MAY 30 2012. (10/08829-6, 07/01306-5, 10/08839-1)