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Landscape-scale exposure to multiazole-resistant Aspergillus fumigatus bioaerosols

Jennifer M. G. Shelton, Johanna Rhodes, Christopher B. Uzzell, Samuel Hemmings, Amelie P. Brackin, Thomas R. Sewell, Asmaa Alghamdi, Paul S. Dyer, Mark Fraser, Andrew M. Borman, Elizabeth M. Johnson, View ORCID ProfileFrédéric B. Piel, View ORCID ProfileAndrew C. Singer, View ORCID ProfileMatthew C. Fisher
doi: https://doi.org/10.1101/2022.11.07.515445
Jennifer M. G. Shelton
1MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
2UK Centre for Ecology & Hydrology, Wallingford, Oxfordshire, UK
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  • For correspondence: jenshe@ceh.ac.uk
Johanna Rhodes
3Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands
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Christopher B. Uzzell
1MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
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Samuel Hemmings
1MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
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Amelie P. Brackin
1MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
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Thomas R. Sewell
1MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
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Asmaa Alghamdi
4School of Life Sciences, University of Nottingham, Nottingham, UK
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Paul S. Dyer
4School of Life Sciences, University of Nottingham, Nottingham, UK
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Mark Fraser
5UK National Mycology Reference Laboratory, National Infections Service, Public Health England, Science Quarter, Southmead Hospital, Bristol, UK
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Andrew M. Borman
5UK National Mycology Reference Laboratory, National Infections Service, Public Health England, Science Quarter, Southmead Hospital, Bristol, UK
6MRC Centre for Medical Mycology, University of Exeter, UK
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Elizabeth M. Johnson
5UK National Mycology Reference Laboratory, National Infections Service, Public Health England, Science Quarter, Southmead Hospital, Bristol, UK
6MRC Centre for Medical Mycology, University of Exeter, UK
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Frédéric B. Piel
7NIHR HPRU in Environmental Exposures & Health, Department of Epidemiology and Biostatistics, Imperial College London, London, UK
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  • ORCID record for Frédéric B. Piel
Andrew C. Singer
2UK Centre for Ecology & Hydrology, Wallingford, Oxfordshire, UK
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Matthew C. Fisher
1MRC Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, UK
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  • ORCID record for Matthew C. Fisher
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Abstract

We demonstrate country-wide exposures to aerosolized spores of a human fungal pathogen, Aspergillus fumigatus, that has acquired resistance to first line azole clinical antifungal drugs. Assisted by a network of citizen scientists across the United Kingdom, we show that 1 in 20 viable aerosolized spores of this mold are resistant to the agricultural fungicide tebuconazole and 1 in 140 spores are resistant to the four most used azoles for treating clinical aspergillosis infections. Season and proximity to industrial composters were associated with growth of A. fumigatus from air samples, but not with the presence of azole resistance, and hotspots were not stable between sampling periods suggesting a high degree of atmospheric mixing. Genomic analysis shows no distinction between those resistant genotypes found in the environment and in patients, indicating that ~40% (58/150 sequenced genomes) of azole-resistant A. fumigatus infections are acquired from environmental exposures. Due to the ubiquity of this measured exposure, it is crucial that we determine source(s) of azole-resistant A. fumigatus, who is at greatest risk of exposure and how to mitigate these exposures, in order to minimize treatment failure in patients with aspergillosis.

One sentence summary UK-wide citizen science surveillance finds a ubiquitous exposure to aerosolized spores of a human fungal pathogen that have evolved in the environment cross-resistance to essential clinical antifungal drugs

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • In the last line of Methods section "Identification of A. fumigatus cyp51A gene azole-resistance alleles" one of the sequencing primers has been replaced with its reverse compliment, such that one primer sequences forward and the other primer sequences in reverse to capture the entire cyp51a coding region.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 29, 2022.
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Landscape-scale exposure to multiazole-resistant Aspergillus fumigatus bioaerosols
Jennifer M. G. Shelton, Johanna Rhodes, Christopher B. Uzzell, Samuel Hemmings, Amelie P. Brackin, Thomas R. Sewell, Asmaa Alghamdi, Paul S. Dyer, Mark Fraser, Andrew M. Borman, Elizabeth M. Johnson, Frédéric B. Piel, Andrew C. Singer, Matthew C. Fisher
bioRxiv 2022.11.07.515445; doi: https://doi.org/10.1101/2022.11.07.515445
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Landscape-scale exposure to multiazole-resistant Aspergillus fumigatus bioaerosols
Jennifer M. G. Shelton, Johanna Rhodes, Christopher B. Uzzell, Samuel Hemmings, Amelie P. Brackin, Thomas R. Sewell, Asmaa Alghamdi, Paul S. Dyer, Mark Fraser, Andrew M. Borman, Elizabeth M. Johnson, Frédéric B. Piel, Andrew C. Singer, Matthew C. Fisher
bioRxiv 2022.11.07.515445; doi: https://doi.org/10.1101/2022.11.07.515445

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