Paracoccidioides brasiliensis is the causal agent of paracoccidioidomycosis (PCM), one of the most important human systemic mycosis in Latin America. P. brasiliensis is a soil fungus that undergoes a dimorphic switch following host inhalation, due to increased temperature. It is estimated that about 10 million people are infected in South America. The annual incidence rate in Brazil is 10-30 infections per million inhabitants, and the mean mortality rate is 1.4 per million per year. The comparative Paracoccidioides project is funded by NIAID through the "Comparative Genomics of Coccidioides and other Pathogenic Dimorphic Fungi" whitepaper. This project aims to examine diversity between three Paracoccidioides strains and determine the common and unique features among the larger group of dimorphic fungal pathogens.
What is Paracoccidioides brasiliensis?
Paracoccidioides brasiliensis is the causal agent of paracoccidioidomycosis (PCM), one of the most important human systemic mycosis in Latin America (Restrepo et al. 2001). It is estimated that about 10 million people are infected in South America (Brummer et al. 1993). Most of these infections occur in Central and South America, particularly in Brazil, Venezuela, and Colombia. The annual incidence rate in Brazil is 10-30 infections per million inhabitants, and the mean mortality rate is 1.4 per million per year (Restrepo et al. 2001). PCM is a granulomatous disease that produces a primary pulmonary infection. In addition, disseminated forms may also be observed. The reticuloendothelial system, skin, mucous membranes and lymph nodes are frequently affected in cases of disseminated disease.
Paracoccidioides brasiliensis has shown extensive genetic variability when analyzed by molecular tools, such as random amplified polymorphic DNA, restriction fragment length polymorphism (Nino-Vega et al. 2000, Soares et al. 1995), and karyotyping by electrophoresis (Feitosa et al. 2003, Montoya et al. 1997). Three distinct lineages, S1, PS2, and PS3 , were recognized using a combined data set of eight regions in five nuclear loci (Matute et al. 2006). A major group (S1) consists of isolates from Brazil, Argentina, Venezuela, Peru and Paraguay. Colombian isolates formed a separate group, PS3. PS2 represents a cryptic phylogenetic species of P. brasiliensis (so far, six isolates from Brazil and Venezuela).
The two sympatric lineages, S1 and PS2, occur within the same geographical regions, suggesting barriers to gene flow other than geographic isolation. The genetic variation is also reflected at the PbGP43 gene (Morais et al. 2000), a specific diagnostic antigen involved in both cellular and humoral responses, protection against murine paracoccidioidomycosis (PCM) and adhesion. The PS2 isolates, Pb2, Pb3 and Pb4, contain highly substituted PbGP43 sequences (14 substitutions). The substitutions result in the basic gp43 protein in the PS2 isolates, in contrast to the neutral or mildly acid gp43 in other isolates. The immune responses elicited by such basic gp43 were richer in IgG2a, IgG2b and IgG3, suggesting a Th1 predominant type of host immunity. The other isolates evoked mostly an IgG1 and IgA, which reflect a Th2-driven response. As a result, PS2 isolates provoked only mild infection when testing the host/parasite relationship in the B10. A mouse model (sensitive to paracoccidioidomycosis).
In addition, isolate Pb01, the most thoroughly studied isolate at the molecular level, does not cluster together with any of these three phylogenetic groups (Molinari-Madlum et al. 1999) and was more recently reclasified as P. lutzii. Molecular advances in the field have produced significant reports on transcript characterization of this pathogen and further confirmed the genetic and metabolic diversity shown by Paracoccidioides in its multiple isolates.
The images in the top banner depict, from left to right, the change from filamentous form to pathogenic form of P. brasiliensis.
Pictures 1 and 4: Dr. Antonio Bretaña and Dr. Gioconda San-Blas
Pictures 2, 3, and 5: Dr. Juan McEwen.
Almeida, A. J., Matute, D. R., Carmona, J. A., Martins, M., Torres, I., McEwen, J. G., Restrepo, A., Leao, C., Ludovico, P., Rodrigues, F., 2007. Genome size and ploidy of Paracoccidioides brasiliensis reveals a haploid DNA content: flow cytometry and GP43 sequence analysis. Fungal Genet Biol. 44, 25-31.
Brummer, E., Castaneda, E., Restrepo, A., 1993. Paracoccidioidomycosis: an update. Clin Microbiol Rev. 6, 89-117.
Calich, V. L., Kashino, S. S., 1998. Cytokines produced by susceptible and resistant mice in the course of Paracoccidioides brasiliensis infection. Braz J Med Biol Res. 31, 615-623.
Carvalho, K. C., Ganiko, L., Batista, W. L., Morais, F. V., Marques, E. R., Goldman, G. H., Franco, M. F, Puccia, R., 2005. Virulence of Paracoccidioides brasiliensis and gp43 expression in isolates bearing known PbGP43 genotype. Microbes Infect. 7, 55-65.
Feitosa Ldos, S., Cisalpino, P. S., dos Santos, M. R., Mortara, R. A., Barros, T.F., Morais, F. V., Puccia, R., da Silveira, J. F., de Camargo, Z. P. , 2003. Chromosomal polymorphism, syntenic relationships, and ploidy in the pathogenic fungus Paracoccidioides brasiliensis. Fungal Genet Biol. 39, 60-69.
Felipe, M. S., Torres, F. A., Maranhao, A. Q., Silva-Pereira, I., Pocas-Fonseca, M. J., Campos, E. G., Moraes, L. M., Arraes, F. B., Carvalho, M. J., Andrade, R. V., Nicola, A. M., Teixeira, M. M., Jesuino, R. S., Pereira, M., Soares, C. M., Brigido, M. M., 2005, Functional genome of the human pathogenic fungus Paracoccidioides brasiliensis. FEMS Immunol Med Microbiol. 45, 369-381.
Matute, D. R., Sepulveda, V. E., Quesada, L. M., Goldman, G. H., Taylor, J.W., Restrepo, A., McEwen, J.G. , 2006. Microsatellite analysis of three phylogenetic species of Paracoccidioides brasiliensis. J Clin Microbiol. 44, 2153-2157.
Montoya, A. E., Moreno, M. N., Restrepo, A., McEwen, J.G., 1997. Electrophoretic karyotype of clinical isolates of Paracoccidioides brasiliensis. Fungal Genet Biol. 21, 223-227.
Nino-Vega, G.A., Calcagno, A.M., San-Blas, G., San-Blas, F., Gooday, G.W., Gow, N.A., 2000. RFLP analysis reveals marked geographical isolation between strains of Paracoccidioides brasiliensis. Med Mycol. 38, 437-441.
Nunes, L. R., Costa de Oliveira, R., Leite, D. B., da Silva, V. S., dos Reis Marques, E., da Silva Ferreira, M. E., Ribeiro, D. C., de Souza Bernardes, L. A., Goldman, M. H., Puccia, R., Travassos, L. R., Batista, W. L., Nobrega, M. P., Nobrega, F. G., Yang, D. Y., de Braganca Pereira, C. A., Goldman, G. H., 2005. Transcriptome analysis of Paracoccidioides brasiliensis cells undergoing mycelium-to-yeast transition. Eukaryot Cell. 4, 2115-2128.
Restrepo, A., McEwen, J.G.,Castaneda, E., 2001. The habitat of Paracoccidioides brasiliensis: how far from solving the riddle? Med Mycol. 39, 233-241
Soares, C. M., Madlun, E. E, da Silva, S.,P, Pereira, M., Felipe, M. S., 1995. Characterization of Paracoccidioides brasiliensis isolates by random amplified polymorphic DNA analysis. J Clin Microbiol. 33, 505-507.
Data access and Citation
The genome sequences of Paracoccidioides are available in GenBank (accession numbers: Paracoccidioides lutzii Pb01 (ABKH00000000), Paracoccidioides brasiliensis Pb03 (ABHV00000000), and Paracoccidioides brasiliensis Pb18 (ABKI00000000)). Data files formerly available on this website can be accessed on our fungal ftp site.
For use of this data, please cite:
Desjardins et al. 2011. "Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis" PLoS Genetics. 7 (10), e1002345.