Imperial College London
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DrJohannaRhodes

Faculty of Medicine, School of Public Health

Honorary Research Fellow
 
 
 
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Contact

 

johanna.rhodes

 
 
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Location

 

Desk 17Sir Michael Uren HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{Sewell:2019:10.1128/mBio.00392-19,
author = {Sewell, T and Zhu, J and Rhodes, J and Hagen, F and Mels, JF and Fisher, M and Jombart, T},
doi = {10.1128/mBio.00392-19},
journal = {mBio},
title = {Non-random distribution of azole resistance across the global population of Aspergillus fumigatus},
url = {http://dx.doi.org/10.1128/mBio.00392-19},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The emergence of azole resistance in the pathogenic fungus Aspergillus fumigatus has continued to increase, with the dominant resistance mechanisms, consisting of a 34-nucleotide tandem repeat (TR34)/L98H and TR46/Y121F/T289A, now showing a structured global distribution. Using hierarchical clustering and multivariate analysis of 4,049 A. fumigatus isolates collected worldwide and genotyped at nine microsatellite loci using analysis of short tandem repeats of A. fumigatus (STRAf), we show that A. fumigatus can be subdivided into two broad clades and that cyp51A alleles TR34/L98H and TR46/Y121F/T289A are unevenly distributed across these two populations. Diversity indices show that azole-resistant isolates are genetically depauperate compared to their wild-type counterparts, compatible with selective sweeps accompanying the selection of beneficial mutations. Strikingly, we found that azole-resistant clones with identical microsatellite profiles were globally distributed and sourced from both clinical and environmental locations, confirming that azole resistance is an international public health concern. Our work provides a framework for the analysis of A. fumigatus isolates based on their microsatellite profile, which we have incorporated into a freely available, user-friendly R Shiny application (AfumID) that provides clinicians and researchers with a method for the fast, automated characterization of A. fumigatus genetic relatedness. Our study highlights the effect that azole drug resistance is having on the genetic diversity of A. fumigatus and emphasizes its global importance upon this medically important pathogenic fungus.IMPORTANCE Azole drug resistance in the human-pathogenic fungus Aspergillus fumigatus continues to emerge, potentially leading to untreatable aspergillosis in immunosuppressed hosts. Two dominant, environmentally associated resistance mechanisms, which are thought to have evolved through selection by the agricultural application of azole fungic
AU  - Sewell,T
AU  - Zhu,J
AU  - Rhodes,J
AU  - Hagen,F
AU  - Mels,JF
AU  - Fisher,M
AU  - Jombart,T
DO  - 10.1128/mBio.00392-19
PY  - 2019///
SN  - 2150-7511
TI  - Non-random distribution of azole resistance across the global population of Aspergillus fumigatus
T2  - mBio
UR  - http://dx.doi.org/10.1128/mBio.00392-19
UR  - http://hdl.handle.net/10044/1/70233
VL  - 10
ER  -
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