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Molecular characterization of genes involved in the pathogeneticity/virulence in the pathogenetic fungus Paracoccidioides brasiliensis

Abstract

Paracoccidioloes brasiliensis, a thermodimorphic fungus, is the causative agent of the prevalent systemic mycosis in Latin America, paracoccidioidomycosis (PCM). Recently, our group presented a survey of expressed genes in the yeast pathogenic phase of P. brasiliensis. We obtained 13,490 ESTs from both 5' and 3'- ends. Clustering analysis yielded the partial sequences of 4,692 expressed genesthat were functionally classified by similarity to known genes. Our results suggest the possible conservation of pathogenicity/virulence mechanisms among fungi, expand considerably gene identification in P. brasiliensis and provide a broader basis for further progress in understanding its biological peculiarities. This type of genomic approach, coupled with transcriptional profiling by microarrays and proteomics may represent an efficient alternative to identify genes involved in virulence/pathogenicity and provide a wider platform for a better understanding of P. brasiliensis biology and the role of several genes during the dimorphic transition and the onset of virulence/pathogenicity in paracoccidioidomycosis. The main objectives of this project are the molecular characterization of genes involved in the process of pathogenicity/virulence of the human pathogenic fungus P. brasiliensis. The specific objectives are: 1) the establishment of a microarray with about 5,000 P. brasiliensis genes; 2) the establishment of a microarray with about 16,000 mouse genes; 3) identification of cDNAs expressed in the pathogenic P. brasiliensis yeast phase by using Suppression Subtraction Hybridization-SSH; 4) quantification by using Real-time RTPCR of the expression of selected genes from itens 1 to 3; 5) sequencing and annotation of the P. brasileinsis mitochondrial genome; 6) to study the variability of the mitochondrial genome in different P. brasiliensis isolates; 7) to sequence 10,000 P. brasiliensis RSTs (Random Sequence Tags); 8) to study functional aspects of genes associtated to the mitochondrial function in P. brasiliensis and 9) to use P. brasiliensis genes that encodes adhesion factors (for example, gp43) or new virulence factors as inducers of imunological protection through DNA vaccines. (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)
BANDEIRA, SIMONE C. B.; NOBREGA, MARINA P. Characterization of Paracoccidioides brasiliensis COX9, COX12, and COX16 respiratory genes. MYCOLOGICAL RESEARCH, v. 112, n. 12, p. 1414-1420, DEC 2008. Web of Science Citations: 2.

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