Molecular characterization of mechanisms involved in pathogenicity and cell signaling in fungi

Abstract

Dermatophytes are filamentous fungi that use keratin as a nutrient source during infection of skin, nail and hair. Dermatophyte adherence and secretion of enzymes are key factors in the colonization of the host tissues, which can be regulated in response to phosphate levels, different carbon and nitrogen sources, and ambient pH. Dermatophytoses constitute one of the most common fungal infections. Despite its clinical importance, the molecular aspects concerning colonization, influence of various environmental factors, gene regulation of enzyme secretion, and drug resistance are not yet fully elucidated. The main goal of this proposal is the understanding of mechanisms used by dermatophytes, especially Trichophyton rubrum, during the colonization of the host tissue, and the signaling pathways involved in sensing, and in transduction of molecular signals in response to the environment. It is intended to assess the relationship between alternative splicing events and response to cytotoxic drugs; to identify genes and non-coding RNAs potentially involved in the pathogenicity of dermatophytes, and to understand the molecular mechanisms involved in sensing and modulation of gene expression that allow fungi to survive under stressful environments, such as extremes of pH, nutrient deprivation, and interaction with host molecules in vitro. Thus, it is expected to reveal molecular mechanisms involved in gene expression regulation, as well as alternative forms of regulation involving ncRNA and mRNA isoforms required for dermatophytes adaptation to adverse environmental conditions such as antifungal drugs and interaction with the host as well as the relationship between different signaling and metabolic pathways that allow the survival of fungi under such conditions. (AU)