Common and cryptic Aspergillus species – one health pathogens

Abstract

Fungal Aspergillus species cause invasive and chronic disease in humans and other animals. This thesis investigated cryptic and common Aspergillus species in A. section Fumigati; their prevalence in Australia and virulence factors impacting the efficacy of the most commonly used antifungal drugs, triazoles. An environmental (soil and air) investigation of 104 Aspergillus isolates for cryptic A. sect. Fumigati species, focusing on the A. viridinutans species complex (AVSC), found a moderate risk of exposure to known pathogenic and cryptic species, but low risk AVSC exposure in indoor and outdoor domestic environments. A new AVSC species was discovered, A. frankstonensis (morphology; ITS region, BenA, CalM, MCM7, actin and RPB2 gene sequencing; antifungal susceptibility; and extrolite analysis are described). Sequencing (ITS, BenA) of clinical isolates from captive birds (n=30) identified A. fumigatus as the most common cause of disease and A. restrictus as pathogenic. Triazole resistance amongst A. fumigatus isolates from clinical and environmental samples is documented over two studies, identifying a low prevalence in Australia. The first investigated pathogenic A. fumigatus isolates from dogs and cats (n=50), finding triazole resistance in one Australian isolate from a dog in the early 1990’s (Sensititre™ YeastOne™YO8). The second investigated clinical (148 human, 21 veterinary) and environmental (n=185) Australian isolates (VIPcheck™ and Sensititre™ YeastOne™ YO10), confirming triazole resistance in three human origin isolates, associated with cyp51A mutations TR34/L98H and G54R. Triazole susceptibility (CLSI) of 37 AVSC isolates were investigated, detecting high triazole minimum inhibitory concentrations (84% of isolates). Compared to wild-type A. fumigatus, high rates of cyp51A mutations were detected on sequencing; however protein homology modelling did not confer resistance. This research informs our understanding of A. sect. Fumigati pathogens in Australia.