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...
Saved in:
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | Article |
Language: | English |
Published: |
2022
|
Subjects: | |
Online Access: | https://hdl.handle.net/10356/163382 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
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 |