Identifying Candida auris transmission in a hospital outbreak investigation using whole-genome sequencing and SNP phylogenetic analysis

Abstract

Candida auris poses a global public health challenge, causing multiple outbreaks within healthcare facilities. Despite advancements in strain typing for various infectious diseases, a consensus on the genetic relatedness threshold for identifying C. auris transmission in local hospital outbreaks remains elusive. We investigated genetic variations within our local isolate collection using whole-genome-based single nucleotide polymorphism (SNP) phylogenetic analysis. A total of 74 C. auris isolates were subjected to whole-genome sequencing (WGS) and SNP phylogenetic analysis via the QIAGEN CLC Genomics Workbench. Isolates included known related strains from the same patient, strains from different hospitals, strains from our hospital patients with no epidemiological link, and 19 patient isolates from a recent C. auris outbreak. All but three isolates were identified to be Clade IV. By examining the genetic diversities of C. auris within patients and between patients, we identified a SNP variation range of 0-13 for identifying related isolates. During an outbreak investigation, utilizing this range, maximum likelihood phylogenetic analysis revealed two distinct clusters that aligned with the epidemiological links. Determining a SNP variation range to delineate genetic relatedness among isolates is crucial for the application of WGS and SNP phylogenetic analysis in identifying C. auris transmission during hospital outbreak investigations. The use of WGS SNP phylogenetic analysis via the CLC Genomics Workbench has emerged as a valuable method for typing C. auris in clinical microbiology laboratories.

Keywords: Candida auris; WG-SNP; anti-fungal susceptibilities; outbreak; strain typing.

FIG 1

Genetic differences measured by pairwise SNP distance between isolates from the same individuals, non-NMH patients, or patients with C. auris colonization or infection upon admission. Boxes indicate mean and 95% confidence interval. Highly distant isolates defined as the isolates with pairwise distance greater than 100 SNPs from others are excluded.

FIG 2

Phylogenetic tree for isolates from the patients involved in C. auris CTICU outbreak identifies two genetically related clusters (numbered and boxed by red or purple dash lines). Within Cluster I, pairwise SNP distances range from 0 to 12, while within Cluster II, distances range from 0 to 4. Unrelated isolates (1, 7, 8, 10, 17, 20) exhibit SNP distances ranging from 18 to 57. The SNP distances between isolates of cluster I and cluster II exceed 27.