Virulence factors of fungal pathogens

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Fungi are important in biotechnology, agriculture and in medicine. Aspergillus species and members of the group Mucorales are filamentous fungi (moulds) that may cause life-threatening disease in susceptible people. Immunosuppressed individuals are at highest risk. Exposure is via airborne fungal spores followed by growth of the fungus in the lung. In some cases, the fungi may spread to other organs such as the brain. Mortality from these infections ranges from 30-80%. Our research is focussed on two aspects of fungal biology: 1) the role of specific sugars present on the fungal spores, called sialic acids, in the adherence of spores to lung tissue, and 2) how fungi acquire iron from the host. During previous NSERC funding, we identified the enzyme in Aspergillus fumigatus that releases sialic acids from tissue. We also showed that iron uptake by Aspergillus fumigatus is mediated by small iron chelators called siderophores, and that siderophore synthesis by fungi is absolutely required for virulence. We characterized the proteins involved in siderophore synthesis and uptake to determine how these proteins bring iron into the fungal cell. We propose to continue working on both of these topics. Specifically, we will probe the role of sialic acids by creating mutant strains that have have no sialic acids on the spore surface. In addition, we will examine the importance of siderophores in the survival of Mucorales and in another species of Aspergillus called Aspergillus terreus. This work will expand our knowledge of the biology of filamentous fungi. A better understanding of the processes of iron acquisition and sialic acid synthesis may ultimately lead to the improvements in the use of these fungi for biotechnology, and in the development of novel, effective antifungal agents.