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

Author(s)

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

• Document type: Journal article
• Source: CURRENT RESEARCH IN MICROBIAL SCIENCES; v. 3, p. 11-pg., 2022-01-01.

Abstract

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)

• FAPESP's process: 15/23435-8 - Molecular mechanisms involved in resistance and adaptive response to fungal inhibitors
• Grantee: Tamires Aparecida Bitencourt
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 09/08411-4 - Functional characterization of genes from the pathogenic fungus Trichophyton rubrum during interaction with host microenvironment cells and molecules.
• Grantee: Nalu Teixeira de Aguiar Peres
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 19/22596-9 - Molecular mechanisms associated with pathogenicity and resistance in fungi: strategies for treating dermatophytosis
• Grantee: Nilce Maria Martinez-Rossi
• Support Opportunities: Research Projects - Thematic Grants