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Tipo do documento: Artigo
Título: Transcriptional profile of the human pathogenic fungus Paracoccidioides lutzii in response to sulfamethoxazole
Autor: Carvalho, Patríıcia Fernanda Zambuzzi
Fernandes, Amanda Gregorim
Valadares, Marize Campos
Tavares, Patricia de Mello
Nosanchuk, Joshua Daniel
Soares, Célia Maria de Almeida
Pereira, Maristela
Abstract: Paracoccidioidomycosis (PCM) is the most prevalent mycosis in Latin America and is caused by a group of fungi within the Paracoccidioides genus. The disease may present clinical and pathological manifestations ranging from asymptomatic pneumonia pulmonary lesions, to disseminated forms involving multiple organs. Sulfonamides were the first drugs used to treat PCM and are still used against this fungal infection. Sulfa drugs are competitive antagonists of ρ-aminobenzoic acid (PABA), a reaction catalyzed by dihydropteroate synthase (DHPS). However, the molecular effects of sulfonamides against the Paracoccidioides genus are unknown. The aim of this work was to investigate the global mechanism of action of sulfamethoxazole on Paracoccidioides lutzii. Yeast cells were grown on minimum medium in the presence or absence of sulfamethoxazole to construct EST libraries. The representational difference analysis (RDA) technique was used to identify up- and down-regulated P. lutzii genes after treatment with sulfamethoxazole. Approximately six transcripts related to mitochondrial function were differentially expressed. To confirm the RDA and bioinformatics results, several relevant genes were studied with quantitative real-time polymerase chain reaction (qRT-PCR) to evaluate their levels of expression. To confirm the impact of sulfamethoxazole on mitochondria, we measured the reduction of tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) by P. lutzii with or without exposure to the drug. MTT assays reveal that sulfamethoxazole produces a marked dose-dependent adverse effect on P. lutzii. The transcriptional activity of selected genes in infected macrophages corroborated our in vitro results. The results indicated that sulfamethoxazole acts in P. lutzii as a competitor for amino acid, nucleic acids and folate cofactor biosynthesis, disrupting mitochondrial functions.
Palavras-chave: Paracoccidioides lutzii
Representational difference analysis
País: Gra-bretanha
Unidade acadêmica: Faculdade de Farmácia - FF (RG)
Citação: ZAMBUZZI-CARVALHO, Patrícia Fernanda et al. Transcriptional profile of the human pathogenic fungus Paracoccidioides lutzii in response to sulfamethoxazole. Medical Mycology, Oxford, v. 53, n. 5, p. 477-492, 2015.
Tipo de acesso: Acesso Aberto
Identificador do documento: 10.1093/mmy/myv011
Identificador do documento: 10.1093/mmy/myv011
Data de publicação: 2015
Aparece nas coleções:FF - Artigos publicados em periódicos

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