Elevated prevalence of azole resistant Aspergillus fumigatus in urban versus rural environments in the United Kingdom

Abstract

Azole resistance in the opportunistic pathogen Aspergillus fumigatus is increasing, dominated primarily by two environmentally-associated resistance alleles: TR34/L98H and TR46/Y121F/T289A. Using an environmental sampling strategy across the South of England we assess the prevalence of azole resistant A. fumigatus (ARAf) in soil samples collected in both urban and rural locations. We characterise the susceptibility profiles of the resistant isolates to three medical azoles, identify the underlying genetic basis of resistance and investigate their genetic relationships. ARAf was detected in 6.7% of the soil samples, with a higher prevalence in urban (13.8%) compared to rural (1.1%) locations. Nineteen isolates were confirmed to exhibit clinical breakpoints for resistance to at least one of three medical azoles, with 18 isolates exhibiting resistance to itraconazole, four to voriconazole, with two also showing additional elevated minimum inhibitory concentration to posaconazole. Thirteen of the resistant isolates harboured the TR34/L98H resistance allele and six isolates carried TR46/Y121F/T289A allele. The 19 azole-resistant isolates were spread across five csp1 genetic subtypes, t01, t02, t04B, t09 and t18 with t02 the predominant subtype. Our study demonstrates that ARAf can be easily isolated in the South of England, especially in urban city centres, which appear to play an important role in the epidemiology of environmentally-linked drug resistant A. fumigatus.