Functional and comparative genomics in fungi

Abstract

Most microorganisms have evolved signal transduction networks that enable them to survive under conditions of nutrient-limited growth, in the presence of antimicrobial drugs, and during the stressful interaction with the host, among others. The depression of this metabolic machinery also responds to environmental pH signaling, an adaptive response possibly involved in fungal pathogenicity. We described that the dermatophyte Trichophyton rubrum raises the culture Ph from an acidic to an alkaline environment during cultivation on queratinized substrates. This shift in the culture pH seems to be determinant for the successful infection process, when the fungus is facing the acidic pH of the human skin. Several genes that respond to the pH environment. Including the pacC gene that encodes a protein homologous to the PacC/Rim101p family of pH signaling transcription regulators, were identified in the model fungi Aspergillus nidulans and Neurospora crassa, as well as in the dermatophyte T. rubrum. The function of most of these genes was identified, but many points of the processes of interaction between them are still not clear. Our proposal is to examine t. rubrum transcriptional profile during its interaction with human skin cells and other molecules present in the host; understand the molecular mechanisms involved in the environment pH sensing and their role in pathogenicity; identify novel molecular mechanisms involved in resistance and adaptation to fungal inhibitors and, consequently, contribute to the control of fungal infection. (AU)