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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2009.tde-04122009-132025
Document
Author
Full name
João Paulo Theophilo Di Benedette
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Campos, Claudia Barbosa Ladeira de (President)
Barros, Mário Henrique de
Puccia, Rosana
Title in Portuguese
Caracterização molecular das subunidades catalítica e regulatória da calcineurina no fungo patogênico Paracoccidioides brasiliensis.
Keywords in Portuguese
Paracoccidioides brasiliensis
Cálcio
Diferenciação microbiana
Fungos
Parasitologia
Transdução de sinal celular
Virulência
Abstract in Portuguese
A calcineurina é uma fosfatase ativada por Ca2+ e calmodulina presente em todos os eucariotos que, em fungos, atua na sinalização de eventos em resposta a estímulos do ambiente e tem papel essencial na patogenicidade de fungos causadores de doenças. O Paracoccidioides brasiliensis é um fungo dimórfico causador da paracoccidioidomicose, uma micose sistêmica profunda de importância para a Saúde Pública no Brasil e no restante da América Latina. Neste e em outros fungos dimórficos patogênicos, a transição dimórfica é necessária para o desenvolvimento de patogenicidade, sendo a calcineurina essencial o dimorfismo. Neste trabalho foram caracterizadas as estruturas gênicas das duas subunidades que compõe o heterodímero de calcineurina e sua expressão durante a transição dimórfica. Foram sugeridos possíveis alvos moleculares de interação com a calcineurina através de bioinformática e os níveis de expressão de três deles foram analisados durante a transição dimórfica. Espera-se que este trabalho contribua para uma melhor compreensão dos mecanismos que regulam a transição dimórfica, virulência e patogenicidade em P. brasiliensis e, dessa forma, auxilie no desenvolvimento de novas abordagens terapêuticas contra a paracoccidioidomicose.
Title in English
Molecular characterization of catalytic and regulatory subunits of calcineurina in the pathogenic fungus Paracoccidioides brasiliensis.
Keywords in English
Paracoccidioides brasiliensis
Calcium
Cellular signal transduction
Fungi
Microbial differentiation
Parasitology
Virulence
Abstract in English
The calcineurin is a Ca2+/almodulin-dependent phosphatase present in all eukaryotes. In fungi, it acts as a signaling molecule that works in response to environmental stimuli and has key role in pathogen city of diverse disease-causing fungi. Paracoccidioides brasiliensis is a dimorphic fungus and the etiological agent of paracoccidioidomycosis, a systemic mycosis important to public health in Brazil and other Latin Americans countries. As in other dimorphic pathogenic fungi, the dimorphic transition is necessary for the development of pathogenicity, with calcineurin playing an essential role to the process of dimorphism. In this work we characterized the gene structures of two subunits that make up the calcineurin heterodimer as well as its expression during the dimorphic transition. We raised possible targets for molecular interaction with calcineurin by bioinformatics and the levels of expression of three of them were examined during the dimorphic transition. We expect that this work might contribute to a better understanding of the mechanisms that regulate the dimorphic transition, virulence and pathogenicity in P. brasiliensis and thus help in developing of new therapeutic approaches against paracoccidioidomycosis.
 
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Publishing Date
2010-03-02
 
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