Non-siderophore function of peroxisomes in Histoplasma pathogenesis

About This Grant

PROJECT SUMMARY The fungal pathogen Histoplasma capsulatum infects and thrives within phagocytes of the immune system. Results from a genetic screen indicate that peroxisome organelles play a critical role in facilitating Histoplasma proliferation in macrophages. Preliminary work demonstrated that the known peroxisomal functions of fatty acid β-oxidation, the glyoxylate cycle, and catalase destruction of reactive oxygen are all dispensible for Histoplasma pathogenesis indicating that peroxisomes play a novel role. This proposal will uncover new peroxisome functions by definition of the peroxisome proteome and metabolome in pathogenic-phase fungal cells. Candidate peroxisomal functions will be validated by functional tests to determine their contributions to Histoplasma’s intramacrophage proliferation. This work will uncover new peroxisomal functions and reveal novel mechanisms for fungal exploitation of the macrophage.