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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

RNA-sequencing analysis of Trichophyton rubrum transcriptome in response to sublethal doses of acriflavine

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Autor(es):
Persinoti, Gabriela Felix [1] ; de Aguiar Peres, Nalu Teixeira [1] ; Jacob, Tiago Rinaldi [1] ; Rossi, Antonio [1] ; Vencio, Ricardo Zorzetto [2] ; Martinez-Rossi, Nilce Maria [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Comp & Matemat, BR-14049900 Ribeirao Preto, SP - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: BMC Genomics; v. 15, n. 7 OCT 27 2014.
Citações Web of Science: 7
Resumo

Background: The dermatophyte Trichophyton rubrum is an anthropophilic filamentous fungus that infects keratinized tissues and is the most common etiologic agent isolated in human dermatophytoses. The clinical treatment of these infections is challenging because only few antifungal drugs are commercially available. To understand the mode of action of cytotoxic drugs against fungi, we evaluated the time-dependent effects of acriflavine on T. rubrum transcriptome using high-throughput RNA-sequencing (RNA-seq) technology. Results: RNA-seq analysis generated approximately 200 million short reads that were mapped to the Broad Institute's Dermatophyte Comparative Database before differential gene expression analysis was performed. By employing a stringent cut-off threshold of -1.5 and 1.5 log(2)-fold changes in gene expression, a subset of 490 unique genes were found to be modulated in T. rubrum in response to acriflavine exposure. Among the selected genes, 69 genes were modulated at all exposure time points. Functional categorization indicated the putative involvement of these genes in various cellular processes such as oxidation-reduction reaction, transmembrane transport, and metal ion binding. Interestingly, genes putatively involved in the pathogenicity of dermatophytoses were down-regulated suggesting that this drug interferes with the virulence of T. rubrum. Moreover, we identified 159 novel putative transcripts in intergenic regions and two transcripts in intron regions of T. rubrum genome. Conclusion: The results provide insights into the molecular events underlying the stress responses of T. rubrum to acriflavine, revealing that this drug interfered with important molecular events involved in the establishment and maintenance of fungal infection in the host. In addition, the identification of novel transcripts will further enable the improvement of gene annotation and open reading frame prediction of T. rubrum and other dermatophyte genomes. (AU)

Processo FAPESP: 09/08403-1 - Análise do perfil transcricional do dermatófito Trichophyton rubrum durante a interação com o agente inibidor Acriflavina
Beneficiário:Gabriela Felix Persinoti
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 08/58634-7 - Genômica funcional e comparativa em fungos
Beneficiário:Nilce Maria Martinez-Rossi
Linha de fomento: Auxílio à Pesquisa - Temático