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SPECIAL SESSION: Impacts of agricultural fungicides on clinical anti-fungal resistance - Panel Discussion

Evolution of azole-resistant Aspergillus fumigatus in agricultural and clinical environments
Marin Brewer - University of Georgia.

Azoles are used to treat both plants and people with fungal diseases, but antifungal resistance is developing in both clinical and agricultural environments. The environmental use of azoles is thought to be the driving force for much of the clinical resistance in the human pathogen Aspergillus fumigatus. Our goal was to determine if azole-resistant A. fumigatus was present in sixty agricultural sites in Georgia and Florida where azoles were used, and if so, to identify the molecular mechanism and compare the genetic similarity of resistant agricultural strains with clinical samples. We isolated over 750 A. fumigatus from soil or plant debris from azole-treated fields, with approximately 27% of the strains showing resistance to the fungicide tebuconazole at 3 ?g/mL. However, susceptibility profiling of 105 of the tebuconazole-resistant strains for minimum inhibitory concentrations (MIC) showed that 100 of the strains had MIC values ?1 ?g/mL of itraconazole, yet only 13 of the strains, all with the TR46/Y121F/T289A Cyp51A allele, were above the established clinical epidemiological cutoff for itraconazole (?2 ?g/mL). We genotyped 180 resistant and sensitive strains from agricultural sites and 60 clinical strains with 9 SSR markers and conducted whole genome sequencing on 100 environmental strains. Overall, there was no genetic clustering of agricultural strains by crop or geographic origin, although an azole-resistant lineage was detected. Preliminary results showing signatures of agricultural origins in azole-resistant strains in both the environment and clinic will be discussed.