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Title: Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment
Authors: Rhodes, Johanna
Abdolrasouli, Alireza
Dunne, Katie
Sewell, Thomas R.
Zhang, Yuyi
Ballard, Eloise
Brackin, Amelie P.
van Rhijn, Norman
Chown, Harry
Tsitsopoulou, Alexandra
Posso, Raquel B.
Chotirmall, Sanjay Haresh
McElvaney, Noel G.
Murphy, Philip G.
Talento, Alida Fe
Renwick, Julie
Dyer, Paul S.
Szekely, Adrien
Bowyer, Paul
Bromley, Michael J.
Johnson, Elizabeth M.
Lewis White, P.
Warris, Adilia
Barton, Richard C.
Schelenz, Silke
Rogers, Thomas R.
Armstrong-James, Darius
Fisher, Matthew C.
Keywords: Science::Medicine
Issue Date: 2022
Source: Rhodes, J., Abdolrasouli, A., Dunne, K., Sewell, T. R., Zhang, Y., Ballard, E., Brackin, A. P., van Rhijn, N., Chown, H., Tsitsopoulou, A., Posso, R. B., Chotirmall, S. H., McElvaney, N. G., Murphy, P. G., Talento, A. F., Renwick, J., Dyer, P. S., Szekely, A., Bowyer, P., ...Fisher, M. C. (2022). Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment. Nature Microbiology, 7(5), 663-674.
Journal: Nature Microbiology
Abstract: Infections caused by the fungal pathogen Aspergillus fumigatus are increasingly resistant to first-line azole antifungal drugs. However, despite its clinical importance, little is known about how susceptible patients acquire infection from drug-resistant genotypes in the environment. Here, we present a population genomic analysis of 218 A. fumigatus isolates from across the UK and Ireland (comprising 153 clinical isolates from 143 patients and 65 environmental isolates). First, phylogenomic analysis shows strong genetic structuring into two clades (A and B) with little interclade recombination and the majority of environmental azole resistance found within clade A. Second, we show occurrences where azole-resistant isolates of near-identical genotypes were obtained from both environmental and clinical sources, indicating with high confidence the infection of patients with resistant isolates transmitted from the environment. Third, genome-wide scans identified selective sweeps across multiple regions indicating a polygenic basis to the trait in some genetic backgrounds. These signatures of positive selection are seen for loci containing the canonical genes encoding fungicide resistance in the ergosterol biosynthetic pathway, while other regions under selection have no defined function. Lastly, pan-genome analysis identified genes linked to azole resistance and previously unknown resistance mechanisms. Understanding the environmental drivers and genetic basis of evolving fungal drug resistance needs urgent attention, especially in light of increasing numbers of patients with severe viral respiratory tract infections who are susceptible to opportunistic fungal superinfections.
ISSN: 2058-5276
DOI: 10.1038/s41564-022-01091-2
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Rights: © The Author(s) 2022, corrected publication 2022. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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