The bZIP Ap1 transcription factor is a negative regulator of virulence attributes of the anthropophilic dermatophyte Trichophyton rubrum

Autor(es)

Peres, Nalu T. A. ; Lang, Elza A. S. ; Bitencourt, Tamires A. ; Oliveira, Vanderci M. ; Fachin, Ana Lucia ; Rossi, Antonio ; Martinez-Rossi, Nilce M.

• Tipo de documento: Artigo Científico
• Fonte: CURRENT RESEARCH IN MICROBIAL SCIENCES; v. 3, p. 11-pg., 2022-01-01.

Resumo

nocompromised patients. During infection, T. rubrum invades host cutaneous tissues by adapting to the acidic pH and the innate immune response of the host. Several genes are upregulated during the growth of T. rubrum in substrates found in human tissue, including the ap1 gene, which codes for the transcription factor Ap1. Here, we generated a null mutant strain by deleting the T. rubrum ap1 gene and performed a functional analysis of this gene. Our results showed that the Delta ap1mutant increased its growth in nail fragments and co-cultures with keratinocytes compared to the wild type. Furthermore, the mutant displayed hyperpigmentation, thickening of the conidia cell wall, increased conidia susceptibility to calcofluor-white compared to the wild type, and loss of control of the keratinolytic activity. Although the ap1 gene was upregulated during exposure to the antifungal drugs amphotericin B, nystatin, and terbinafine, its deletion did not alter the fungal susceptibility to these drugs, revealing the role of the ap1 gene in the physiological response to the stress caused by these drugs, but not in their resistance. Moreover, ap1 was also involved in the oxidative stress response caused by menadione, but not paraquat or hydrogen peroxide. These findings indicate that the ap1 gene plays a role in the negative control of virulence-related attributes and may contribute to the chronicity of nail infection caused by T. rubrum. (AU)

• Processo FAPESP: 11/08424-9 - Genômica funcional e comparativa em fungos. Sub projeto: Genômica funcional de Trichophyton rubrum durante interação com pele e unha humana
• Beneficiário: Elza Akie Sakamoto Lang
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/23435-8 - Mecanismos moleculares envolvidos na resistência e na resposta adaptativa a inibidores fúngicos
• Beneficiário: Tamires Aparecida Bitencourt
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/08411-4 - Caracterização funcional de genes do fungo patogênico Trichophyton rubrum durante o processo de interação com células e moléculas do microambiente hospedeiro.
• Beneficiário: Nalu Teixeira de Aguiar Peres
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/22596-9 - Mecanismos moleculares associados à patogenicidade e resistência em fungos: estratégias para o tratamento de dermatofitoses
• Beneficiário: Nilce Maria Martinez-Rossi
• Modalidade de apoio: Auxílio à Pesquisa - Temático