Population Structure and Molecular Epidemiology of the Fungal Pathogen Aspergillus fumigatus at Global and Local Scales

Abstract

Aspergillus fumigatus is an opportunistic fungus known to cause a group of life-threatening infections collectively known as aspergillosis. In this thesis, multilocus sequence and microsatellite markers, among others, were used to study global and local A. fumigatus population structures. We examined the roles of sexual and asexual reproduction in the initiation of azole resistance globally. Furthermore, we investigated the origin of multi-triazole resistance in India and whether the use of fungicides on farms propagates resistance in environmental strains of clinical importance in Hamilton, Ontario. We characterized for the first time the A. fumigatus population in Cameroon while concomitantly screening for environmental resistance. Our results showed that sexual reproduction plays a key role in the development of triazole resistance globally. We found that multi-triazole resistance in India has multiple origins, which include mutational, recombinational and exotic origins. Our results provided little to no evidence that azole fungicides are the origin, or increase the frequency of triazole resistance in clinical A. fumigatus in Hamilton. Additionally, we identified a significantly unique A. fumigatus population in Cameroon. Our findings will potentially contribute towards developing effective long-term management strategies against aspergillosis.