Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Eukaryot Cell ; 4(12): 2115-28, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16339729

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.


Assuntos
Regulação Fúngica da Expressão Gênica , Micélio/citologia , Paracoccidioides/genética , Transcrição Gênica , Leveduras/citologia , 4-Hidroxifenilpiruvato Dioxigenase/antagonistas & inibidores , Técnicas de Cultura de Células , Diferenciação Celular , Meios de Cultura , Cicloexanonas/farmacologia , Inibidores Enzimáticos/farmacologia , Etiquetas de Sequências Expressas , Perfilação da Expressão Gênica , Genes Fúngicos , Humanos , Análise em Microsséries , Estrutura Molecular , Micélio/genética , Micélio/metabolismo , Nitrobenzoatos/farmacologia , Paracoccidioides/citologia , Paracoccidioides/efeitos dos fármacos , Paracoccidioides/metabolismo , Paracoccidioides/patogenicidade , Paracoccidioidomicose/etiologia , Temperatura , Leveduras/efeitos dos fármacos , Leveduras/genética , Leveduras/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...