Aspergillus fumigatus is a globally present opportunistic fungal pathogen that plays a key role in degrading organic matter. A. fumigatus can cause a vast array of diseases, collectively known as aspergilloses. The most serious of these is invasive aspergillosis, that has a mortality rate of 30 to 95% with treatment. Recent studies have indicated that the global A. fumigatus population consists of multiple divergent genetic clusters that are broadly distributed geographically. However, most of the previously analyzed samples have come from continental Eurasia and the Americas where the effects of historical or contemporary gene flow is difficult to distinguish. My thesis project, therefore, focused on analyzing the genetic diversity of the Auckland, New Zealand A. fumigatus population, as it is geographic distant from all previously analyzed populations. Here, we obtained 104 A. fumigatus isolates from Auckland and compared the genotypes of these isolates to population data obtained from nine other countries from Europe, Africa, North America, and Asia. The goal was to analyze the potential effects of historical differentiation and gene flow within this population. We determined that the Auckland population had a low, non-significant level of differentiation compared to most previously surveyed global populations. However, the Auckland population also contained unique genetic elements not present within populations from other geographic regions. Though the hypothesis of random recombination was rejected, we found abundant evidence for phylogenetic incompatibility and recombination within the Auckland A. fumigatus population. Lastly, we identified two triazole resistant strains within the Auckland population, with one carrying the common TR34/L98H cyp51A mutation. Our results suggest that contemporary gene flow, likely due to anthropogenic factors, is a major force shaping the New Zealand A. fumigatus population. These results contribute to our understanding of the high levels of gene flow observed within and among many geographic populations of A. fumigatus. / Thesis / Master of Science (MSc) / Aspergillus fumigatus is a globally distributed fungal mold capable of causing serious diseases in individuals with weakened immune systems or lung damage. In the environment, A. fumigatus lives in the soil where it degrades organic matter and contributes to the cycling of nitrogen and carbon across the planet. Due to the airborne nature of its spores, people inhale this fungus daily, and those at risk may develop disease. These diseases, collectively known as aspergilloses, can result in long term chronic illnesses, and in the case of invasive aspergillosis, the death rate can be as high as 95%, even with treatment. Medical treatment of aspergilloses involves the use of antifungal drugs. However, some A. fumigatus strains have developed resistance. I am interested in the patterns of global genetic diversity of A. fumigatus populations. For my MSc thesis, I investigated the A. fumigatus population within Auckland, New Zealand, as it is both geographically isolated and distant from other previously surveyed populations. Our data illustrated that the New Zealand population contains pockets of unique diversity as well as high levels of similarity to the previously surveyed populations within Europe. My results suggest that human influences, likely due to travel and trade, have played a large role in shaping the genetic diversity of the A. fumigatus population from Auckland, New Zealand.

A thesis submitted to the school of graduate studies in the partial fulfillment of the requirements for the degree doctor of philosophy. / Fungal populations occupy a vast number of ecological niches across many geographic areas around the planet. Fungi act as essential nutrient recyclers, playing key roles as saprophytes, mutualists, and pathogens. As humans, we use these broad properties of fungi in biochemical and pharmaceutical industries, creating a plethora of products ranging from antimicrobials to food products. However, certain fungal species have become a devastating burden on human public health. Of these fungal species, my PhD thesis has focused on the critically important mold Aspergillus fumigatus. This mold is an opportunistic human pathogen, being the leading etiological cause of the spectrum of diseases termed aspergillosis that yearly affects over 8,000,000 people worldwide. In addition, the rising number of antifungal resistant strains around the world, especially within environmental populations, is of critical concern. Given that almost all aspergillosis infections result from environmental strains, and that soil is a major ecological niche for A. fumigatus, my thesis focused on characterizing genetic and phenotypic aspects of soil isolates of A. fumigatus obtained from many geographic and climatic regions around the world. My analyses revealed extensive allelic and genotypic diversity within and among populations. These A. fumigatus populations were defined by both historical differentiations, high gene flow, non-random recombination, and high susceptibility to triazole antifungals. Additionally, I tested the sexual fecundity of a subset of these global strains and found that geographic and genetic distance between the pairs of parental strains had little effect on sexual fecundity. Lastly, my research found broad variations in growth of a global sample of A. fumigatus strains at different temperatures. Again, no relationship of either geographic or genetic distance on strain growth was observed. Overall, my research highlights the extraordinary nature of A. fumigatus populations to quickly spread and adapt across diverse and complex environments. / Thesis / Doctor of Philosophy (PhD) / Aspergillus fumigatus is a cosmopolitan mold that causes opportunistic infections in humans termed aspergillosis. To better understand the environmental reservoirs of aspergillosis infection, I investigated soil populations of this fungus, as soil is likely the largest reservoir of A. fumigatus. I isolated A. fumigatus strains from 11 countries across 6 continents and genetically compared these soil populations to each other and to clinical A. fumigatus populations. I found extensive genetic diversity within most local soil populations, along with different relationships among geographic populations. When a sample of these global strains were sexually crossed, I uncovered high variation in their sexual fecundity, which lowered at higher geographic distances. Lastly, strains exhibited high variations in growth at different temperatures regardless of climatic, genetic, and geographic factors from where they were isolated. My thesis highlights the extraordinary phenotypic variations and complex population structure of A. fumigatus populations isolated from soil across the globe.