Abstract.
Aspergillus fumigatus is a ubiquitous saprotrophic fungus and an opportunistic pathogen in humans and dogs and because of its ubiquity, hundreds of A. fumigatus spores are inhaled on a daily basis. In most cases, the inhalation of spores is harmless but in humans, with an immunodeficiency, an invasive form of pulmonary aspergillosis (IPA) can develop which have a mortality rate of 50% or higher. A. fumigatus can cause also non-invasive sino-nasal aspergillosis (SNA) for example in otherwise immunocompetent dogs. We have compared a set of A. fumigatus isolates from humans with IPA and dogs with SNA with a set of environmental isolates of A fumigatus and a set of A fumigatus type strains.  Tandem repeats in the cyp51A  gene and responsible for azole resistance were only detected in human isolates via qPCR, and in our case, none of the environmental or canine isolates. We investigated whether genotypic and/or phenotypic differences exist between these three groups to determine whether infections are caused by a specific subgroup of A. fumigatus. A phylogenetic inference based on calmodulin(caM) sequences and beta-tubulin(benA) shows no clear distinction between the three groups of isolates. Genotyping and microsatellite analysis shows that that dogs with SNA are infected by one genotype only whereas human patients are infected by various genotypes. Interestingly, the phenotypic analysis indicated that the isolates from dogs are most variable in growth speed and morphology as compared to human and environmental isolates. K-means clustering of the measurements of colony growth in several media made with imageJ showed that one cluster contained mainly canine isolates, as well as the type strain for A. neoellipticus. Moreover, all the environmental and human isolates were distributed among two different clusters from the one that contained canine isolates. Our observation shows that canine isolates are phenotypically more diverse that their environmental and human counterparts. The basis of this heterogeneity might be due to genomic differences or epigenetic variations that might occur during the infection process in dogs. Our results suggest that the canine isolates might represent a subgroup of A. fumigatus that are responsible for SNA

7 / Heterogeneity and within-host adaption observed in clinical isolates of Aspergillus fumigatus