Transcriptome analysis of Paracoccidioides brasiliensis cells undergoing mycelium-to-yeast transition

Transcriptome analysis of Paracoccidioides brasiliensis cells undergoing mycelium-to-yeast transition

Autor Nunes, Luiz R. Google Scholar
Oliveira, Regina Costa de Google Scholar
Leite, Daniela Batista Google Scholar
Silva, Vivian Schmidt da Google Scholar
Marques, Everaldo dos Reis Google Scholar
Ferreira, Marcia Eliana da Silva Google Scholar
Ribeiro, Diogenes Custodio Duarte Google Scholar
Bernardes, Lucian Angelo de souza Google Scholar
Goldman, Maria Helena S Google Scholar
Puccia, Rosana Autor UNIFESP Google Scholar
Travassos, Luiz R. Autor UNIFESP Google Scholar
Batista, Wagner L. Autor UNIFESP Google Scholar
Nobrega, Marina Pasetto Google Scholar
Nobrega, Francisco G. Google Scholar
Yang, Ding Yang Google Scholar
Pereira, Carlos A de Bragança Google Scholar
Goldman, Gustavo H. Google Scholar
Instituição Universidade de São Paulo (USP)
Univ Mogi Das Cruzes
Universidade Federal de São Paulo (UNIFESP)
Univ Vale Paraiba
Tunghai Univ
Resumo Paracoccidioides brasiliensis is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), a systemic mycosis prevalent in South America. in humans, infection starts by inhalation of fungal propagules, which reach the pulmonary epithelium and transform into the yeast parasitic form. Thus, the mycelium-to-yeast transition is of particular interest because conversion to yeast is essential for infection. We have used a P. brasiliensis biochip carrying sequences of 4,692 genes from this fungus to monitor gene expression at several time points of the mycelium-to-yeast morphological shift (from 5 to 120 h). the results revealed a total of 2,583 genes that displayed statistically significant modulation in at least one experimental time point. Among the identified gene homologues, some encoded enzymes involved in amino acid catabolism, signal transduction, protein synthesis, cell wall metabolism, genome structure, oxidative stress response, growth control, and development. the expression pattern of 20 genes was independently verified by real-time reverse transcription-PCR, revealing a high degree of correlation between the data obtained with the two methodologies. One gene, encoding 4-hydroxyl-phenyl pyruvate dioxygenase (4-HPPD), was highly overexpressed during the mycelium-to-yeast differentiation, and the use of NTBC [2-(2-nitro-4-trifluoromethylbenzoyl)-cyclohexane-1,3-dione], a specific inhibitor of 4-HPPD activity, as well as that of NTBC derivatives, was able to inhibit growth and differentiation of the pathogenic yeast phase of the fungus in vitro. These data set the stage for further studies involving NTBC and its derivatives as new chemotherapeutic agents against PCM and confirm the potential of array-based approaches to identify new targets for the development of alternative treatments against pathogenic microorganisms.
Idioma Inglês
Data 2005-12-01
Publicado em Eukaryotic Cell. Washington: Amer Soc Microbiology, v. 4, n. 12, p. 2115-2128, 2005.
ISSN 1535-9778 (Sherpa/Romeo, fator de impacto)
Editor Amer Soc Microbiology
Extensão 2115-2128
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000234032300016

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