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Rapid genome sequencing for outbreak analysis of the emerging human fungal pathogen Candida auris

View ORCID ProfileJohanna Rhodes, View ORCID ProfileAlireza Abdolrasouli, View ORCID ProfileRhys A. Farrer, View ORCID ProfileChristina A. Cuomo, View ORCID ProfileDavid M. Aanensen, View ORCID ProfileDarius Armstrong-James, View ORCID ProfileMatthew C. Fisher, View ORCID ProfileSilke Schelenz
doi: https://doi.org/10.1101/201343
Johanna Rhodes
1Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
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Alireza Abdolrasouli
2National Heart and Lung Institute, Imperial College London, London, United Kingdom
3Department of Medical Microbiology, Charing Cross Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
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Rhys A. Farrer
1Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
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Christina A. Cuomo
4Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
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David M. Aanensen
1Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
5The Centre for Genomic Pathogen Surveillance, Wellcome Trust Genome Campus, Cambridgeshire, UK
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Darius Armstrong-James
2National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Matthew C. Fisher
1Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
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Silke Schelenz
2National Heart and Lung Institute, Imperial College London, London, United Kingdom
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Abstract

Background Candida auris was first described in 2009, and has since caused nosocomial outbreaks, invasive infections and fungaemia across 11 countries in five continents. An outbreak of C. auris occurred in a specialised cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak reported worldwide, involving a total of 72 patients.

Methods To understand the epidemiology of C. auris infection within this hospital, we sequenced the genomes of outbreak isolates using Oxford Nanopore Technologies and Illumina in order to type antifungal resistance alleles and to explore the outbreak within its local and global context.

Findings Phylogenomic analysis placed the UK outbreak in the India/Pakistan clade, demonstrating an Asian origin. The outbreak showed similar diversity to that of the entire clade and limited local spatiotemporal clustering was observed. One isolate displayed resistance to both echinocandins and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FKS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1. These mutations are novel for this pathogen.

Interpretation Multiple differential episodic selection of antifungal resistant genotypes has occurred within a genetically heterogenous population across this outbreak, creating a resilient pathogen and making it difficult to define local-scale patterns of transmission as well as implementing outbreak control measures.

Funding Antimicrobial Research Collaborative, Imperial College London

Copyright 
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 October 13, 2017.
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Rapid genome sequencing for outbreak analysis of the emerging human fungal pathogen Candida auris
Johanna Rhodes, Alireza Abdolrasouli, Rhys A. Farrer, Christina A. Cuomo, David M. Aanensen, Darius Armstrong-James, Matthew C. Fisher, Silke Schelenz
bioRxiv 201343; doi: https://doi.org/10.1101/201343
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Rapid genome sequencing for outbreak analysis of the emerging human fungal pathogen Candida auris
Johanna Rhodes, Alireza Abdolrasouli, Rhys A. Farrer, Christina A. Cuomo, David M. Aanensen, Darius Armstrong-James, Matthew C. Fisher, Silke Schelenz
bioRxiv 201343; doi: https://doi.org/10.1101/201343

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