Functional characterization of the transcription factor ACE2 of the dermatophyte Trichophyton rubrum and its implication in the host-pathogen interaction

Abstract

Dermatophytes are pathogenic fungi that infect keratinized tissues of humans and animals such as skin, hair and nails. The anthropophilic species Trichophyton rubrum is the etiologic agent of higher frequency, which occurs in both immunocompromised patients and healthy individuals, remaining viable in the environment for long periods, which makes the complete elimination of this dermatophyte difficult. The search for new antifungal drugs and new cellular targets is constant, since the misuse of these drugs promotes the selection of resistant organisms, hindering the success of treatment. With the advent of the genome sequencing of several dermatophytes by the Broad Institute/NIH, it is now possible to perform comparative genomic analysis among dermatophytes, guiding studies on the regulation of the expression of genes related to pathogenicity, virulence and environmental adaptation. Thus, drugs that act in the biosynthesis of cell wall are being actively developed, aiming to restrain the colonization and infection of host tissue. Among the transcription factors related to the genes expression regulation of the components of this pathway is the ACE2, which belongs to the Cys2His2 zinc finger family. Interestingly, the transcription factor PacC, a member of that family that is involved in the regulation of gene expression in response to extracellular pH, also participates in processes related to colonization and infection of host tissues, in the expression of virulence factors and morphogenesis of the fungal wall cell. Thus, based on the clinical importance of T. rubrum as the etiologic agent of skin infections, this project aims to assess the functional role of the transcription factors PacC and ACE2, and the possible involvement of ACE2 in the pathogenesis of T. rubrum. Our results will further contribute to the expansion of knowledge related to fungal adaptive responses and the modulation of expression of their genes, as well as the involvement of these transcription factors in remodeling the cell wall under environmental stress, such as the presence of cytotoxic agents, and under different nutrient sources.