Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment

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 presen...

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Main 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.
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2022
Subjects:
Online Access:https://hdl.handle.net/10356/163382
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-163382
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Antifungal Resistance
Aspergillosis
spellingShingle Science::Medicine
Antifungal Resistance
Aspergillosis
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.
Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment
description 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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
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.
format Article
author 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.
author_sort Rhodes, Johanna
title Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment
title_short Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment
title_full Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment
title_fullStr Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment
title_full_unstemmed Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment
title_sort population genomics confirms acquisition of drug-resistant aspergillus fumigatus infection by humans from the environment
publishDate 2022
url https://hdl.handle.net/10356/163382
_version_ 1759852962784477184
spelling sg-ntu-dr.10356-1633822023-03-05T16:53:43Z Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment 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. Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Antifungal Resistance Aspergillosis 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. Published version This study was partially supported by an unrestricted education grant from Gilead Sciences through their investigator sponsored research programme. J. Rhodes, T.S., A.P.B., P.S.D., D.A.J. and M.C.F. were supported by grants from the NERC (nos. NE/P001165/1 and NE/P000916/1), the UK Medical Research Council (MRC) (no. MR/R015600/1) and Wellcome Trust (no. 219551/Z/19/Z). D.A.J. is also funded by the Medical Research Council (grant no. MR/V037315/1) and Cystic Fibrosis Trust (grant no. SRC015). D.A.J. is funded by the Department of Health and Social Care (DHSC) Centre for Antimicrobial Optimisation (CAMO), Imperial College London. The views expressed in this publication are those of the authors and not necessarily those of the DHSC, National Health Service or National Institute for Health Research (NIHR). M.C.F. is a CIFAR Fellow in the Fungal Kingdom programme. K.D. was supported by a PhD studentship awarded by the School of Medicine, Trinity College Dublin. P.G.M. and J. Renwick (Dublin) received a project grant from the National Children’s Hospital, Tallaght University Hospital, which in part supported this work. A.W. and E.B. are supported by the Wellcome Trust Strategic Award (grant no. 097377), MRC Centre for Medical Mycology (grant no. MR/N006364/2) at the University of Exeter and a Biotechnology and Biological Sciences Research Council EASTBIO grant (no. BB/M010996/1). The authors also acknowledge the Imperial College London Cystic Fibrosis Strategic Research Centre and NIHR CAMO. 2022-12-05T05:39:53Z 2022-12-05T05:39:53Z 2022 Journal Article 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. https://dx.doi.org/10.1038/s41564-022-01091-2 2058-5276 https://hdl.handle.net/10356/163382 10.1038/s41564-022-01091-2 35469019 2-s2.0-85128748473 5 7 663 674 en Nature Microbiology © 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/. application/pdf