The function of phosphatase encoding genes in the Aspergillus fumigatus virulence and pathogenicity

Abstract

A. fumigatus is a primary opportunist and pathogen, and an allergenic fungus that also causes asthma and sinusitis in immunocompetent patients. Because A. fumigatus produces great amounts of asexual spores (conidia), the human respiratory tract is continuously exposed to this fungus. The conidia are inhaled and reach the lungs due to their small size; in the alveoli, they become active and germinate. Environmental sensing and the acquisition of essential nutrients from the environment are traits that are associated to the growth of this saprophyte in inhospitable environments. In spite of its medical and ecological importance, the basic biology of this organism is not well understood. The main objectives of this project are: (i) the molecular characterization of genes modulated at the transcriptional level by calcineurin-dependent transcription factor CrzA and that were previously identified by Chromatin Immunoprecipitation followed by DNA sequencing (Chip-Seq); (ii) the molecular characterization of all genes encoding phosphatases in A. fumigatus and their involvement in virulence and pathogenicity; and (iii) the global identification of targets regulated at either transcripcional and/or translational level by these phosphatases. In all these objectives, deletion mutants will be constructed for these genes, their phenotypes, virulence and pathogenicity investigated, both in the alternative model Galleria mellonella, as well as in an aspergillosis mouse model of imunosuppression. (AU)