Citizen Science Surveillance of Triazole-Resistant Aspergillus fumigatus in United Kingdom Residential Garden Soils

Abstract

Compost is an ecological niche for Aspergillus fumigatus due to its role as a decomposer of organic matter and its ability to survive the high temperatures associated with the composting process. Subsequently, composting facilities are associated with high levels of A. fumigatus spores that are aerosolised from compost and cause respiratory illness in workers. In the UK, gardening is an activity enjoyed by individuals of all ages and it is likely that they are being exposed to A. fumigatus spores when handling commercial compost or compost they have produced themselves. In this study, 246 citizen scientists collected 509 soil samples from locations in their garden in the UK, from which were cultured 5,174 A. fumigatus isolates. Of these isolates, 736 (14%) were resistant to tebuconazole: the third most-sprayed triazole fungicide in the UK, which confers cross-resistance to the medical triazoles used to treat A. fumigatus lung infections in humans. These isolates were found to contain the common resistance mechanisms in the A. fumigatus cyp51A gene TR 34 /L98H or TR 46 /Y121F/T289A, and less common resistance mechanisms TR 34 , TR 53 , TR 46 /Y121F/T289A/S363P/I364V/G448S and (TR 46 ) 2 /Y121F/M172I/T289A/G448S. Regression analyses found that soil samples containing compost were significantly more likely to grow susceptible and tebuconazole-resistant A. fumigatus than those that did not, and that compost samples grew significantly higher numbers of A. fumigatus than other samples. Importance These findings highlight compost as a potential health hazard to individuals with pre-disposing factors to A. fumigatus lung infections, and a potential health hazard to immunocompetent individuals who could be exposed to sufficiently high numbers of spores to develop infection. Furthermore, this study found that 14% of A. fumigatus isolates in garden soils were resistant to an agricultural triazole, which confers cross-resistance to medical triazoles used to treat A. fumigatus lung infections. This raises the question of whether compost bags should carry additional health warnings regarding inhalation of A. fumigatus spores, whether individuals should be advised to wear facemasks whilst handling compost or whether commercial producers should be responsible for sterilising compost before shipping. The findings support increasing public awareness of the hazard posed by compost and investigating measures that can be taken to reduce the exposure risk.

The importance of antimicrobial resistance in medical mycology

“…For example, antifungal resistance in Aspergillus fumigatus is clearly associated with environmental selection of resistance as a consequence of exposure to agricultural azoles used in crop protection 13 . Indeed, estimates suggest that one in 20 culturable isolates of this fungus isolated from the air are tebuconazole resistant 14 . Some strains of Candida glabrata, Candida krusei, most strains of Scedosporium and the Mucorales, and the recent emergent species Candida auris display reduced susceptibility to commonly used antifungals.…”

Landscape-scale exposure to multiazole-resistantAspergillus fumigatusbioaerosols

“…However, none of the included environmental variables were found to affect the number of ARAf grown from the air-samples, and the detected clusters were not stable between sampling rounds. In parallel to our aerosol sampling, a soil-sampling campaign was conducted by citizen scientists during the 2019 summer solstice, resulting in the recovery of a high burden of ARAf from garden soils totaling 736 (14%) resistant isolates from 246 locations (8). There were 46 participants from which both soil and at least one air sample were collected (Supplementary Importantly, while our study only reports on aerosolized spores collected in the UK, this exposure is not restricted to the UK.…”

Why have we neglected fungal infections?

“…“Secondly, agriculture uses azole antifungals to protect crops from fungal diseases. Aspergillus in the environment adapts to this exposure and becomes resistant.” Indeed, researchers isolated A. fumigatus resistant to an agricultural azole, which bestows cross‐resistance to medical azole antifungals, from 14% of 509 soil samples from UK residential gardens 4 …”

“…We inhale several hundred A. fumigatus spores a day. 4 Usually, A. fumigatus spores are harmless. But in immunocompromised people and those with chronic lung diseases, aspergillosis can cause serious problems.…”

“…Indeed, researchers isolated A. fumigatus resistant to an agricultural azole, which bestows crossresistance to medical azole antifungals, from 14% of 509 soil samples from UK residential gardens. 4 "The mechanisms driving antifungal resistance depend on the fungus and antifungal," Dr Alastruey-Izquierdo explains. Point mutations (a change to a single nucleotide in the fungal DNA) are the most common causes of resistance in Aspergillus.…”