Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris

Abstract

Candida auris was first described in 2009, and it has since caused nosocomial outbreaks, invasive infections, and fungaemia across at least 19 countries on five continents. An outbreak of C. auris occurred in a specialized cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak in the UK, involving a total of 72 patients. To understand the genetic epidemiology of C. auris infection both within this hospital and within a global context, we sequenced the outbreak isolate genomes using Oxford Nanopore Technologies and Illumina platforms to detect antifungal resistance alleles and reannotate the C. auris genome. Phylogenomic analysis placed the UK outbreak in the India/Pakistan clade, demonstrating an Asian origin; the outbreak showed similar genetic 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 add to a growing body of research on multiple antifungal drug targets in this organism. 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 and implement outbreak control measures.

Diagnosis, management and prevention of Candida auris in hospitals: position statement of the Australasian Society for Infectious Diseases

“…However, WGS has superior discriminative power and is the preferred method for simultaneously identifying and genotyping strains . Long read sequencing has been used to investigate hospital outbreaks . Although WGS can offer a shorter turnaround time (8–72 h) than other typing methods, it requires extra bioinformatic expertise and is more expensive.…”

“…Common misidentifications of Candida auris by commercial phenotypic identification systems18,35,37 Long read sequencing has been used to investigate hospital outbreaks 20,53. Although WGS can offer a shorter turnaround time (8-72 h) than other typing methods, it requires extra bioinformatic expertise and is more expensive.…”

Internal validation of GPS™MONODOSE CanAur dtec‐qPCR kit following the UNE/EN ISO/IEC 17025:2005 for detection of the emerging yeast Candida auris

“…Typing of C. auris isolates by using the MALDI‐TOF MS was found however to be as effective as the gold standards in genetic typing such as amplified fragment length polymorphism (AFLP) and multi‐locus sequence typing (MLST) . Whole Genome Sequencing (WGS) has shown a powerful resolution in identification and typing of C. auris . Recently, Kordalewska et al.…”

“…24,25 Whole Genome Sequencing (WGS) has shown a powerful resolution in identification and typing of C. auris. [26][27][28][29][30] Recently, Kordalewska et al (2017) 19 developed a conventional end-point PCR and melting temperature (Tm) PCR analysis to identify the four species C. auris, C. haemulonii, C. duobushaemulonii and C. lusitaniae. In addition, endpoint PCR and real-time PCR using hydrolysis probes have been reported for detection of C. auris from surveillance samples.…”

Author Correction: Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris

“…Upon publication of the original article 1 the authors were contacted by Dr. Trevor Bedford who has provided invaluable methods to improve the temporal analysis work presented in this paper. Due to conversations with Dr. Bedford the authors improved the calculation of the time to most recent common ancestor (TMRCA) and the clock rate of evolution within Candida auris, to take into account the whole genome, not just the variable sites.…”