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Genomic Analysis of Aspergillus Shows Prevalence of Drug-Resistant Fungal Infections in the UK

NEW YORK— A commonly found fungal pathogen that has developed resistance to agricultural fungicides may be responsible for at least 40 percent of drug-resistant aspergillosis cases across the UK, a new study has found.

In a paper published in Science Advances on Friday, a team led by researchers from Imperial College London described its analysis of Aspergillus fumigatus from air samples collected across the UK. This fungus is released into the air when soil and other organic matter decomposes and is responsible for a human tract respiratory tract infection called aspergillosis, which usually affects immunocompromised patients. The disease can be fatal if left untreated.

Aspergillus has become increasingly resistant to azole antifungals – the most common treatment for aspergillosis – and recent studies suggest that growing azole-based agricultural fungicides may be driving this resistance. That environmentally derived resistance could also contribute to aspergillosis treatment failure in humans. However, the authors said little is known about the extent to which people in the UK are exposed to azole-resistant A. fumigatus (ARAf).

To procure samples from across the country, Jennifer Shelton, a researcher at Imperial College London, put out an online advertisement on social media platforms asking citizens to collect air samples at home. "People from Scotland to Wales and the bottom of the UK responded," she said.

Shelton sent plates that could trap the fungal spores and asked the 485 participants to place them near their windowsills on specified days and mail them back. The participants collected 1,894 passive air samples on four days over a year: once each in the summer, autumn, winter, and spring, from 2018 to 2019.

In the lab, the researchers incubated the samples at 43°C, a highly selective temperature for A. fumigatus, and identified 2,366 Aspergillus colonies from 919 samples. Of those identified, 99 isolates were resistant to the common fungicide tebuconazole. The researchers also found that most of these colonies were resistant to drugs used in the clinic to treat aspergillosis infections, including itraconazole and voriconazole.

The researchers additionally genotyped these environmental samples to examine the genetic basis of their tebuconazole resistance. Azole resistance is typically conferred by mutations within the sterol-demethylase gene cyp51A.

But from this, the researchers reported that 30 percent of the tebuconazole-resistant isolates did not contain any polymorphisms in the cyp51A promoter or coding regions, suggesting the existence of alternative resistance mechanisms. The authors said this was a matter of concern as only a few mutations can be detected by the currently available PCR diagnostic methods.

By comparing their environmental samples to previously published data on patients with aspergillosis, the researchers found that the hallmarks of resistance in their samples were also present in patients. The authors estimated that nearly 40 percent of ARAf infections in patients are acquired from environmental exposure.

While this study only reported aerosolized spores collected in the UK, the authors noted that the exposure is not restricted to the UK. Recruitment of citizen scientists attracted several participants from outside the UK, and air samples from Germany, France, and the Netherlands also grew viable ARAf.

According to Shelton, the next steps are mapping out the landscapes, gardens, and construction sites that could be the potential source of these spores. "Once we know that, we can advise people on how to minimize the exposure to prevent infections," she said.