Whole genome sequencing analysis demonstrates therapy‐induced echinocandin resistance in Candida auris isolates

Abstract

Candida auris is an emerging, multidrug‐resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra‐patient resistance development, whole genome sequencing (WGS) single‐nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin‐resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17–127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1–10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin‐resistant strains are capable of long‐term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross‐infect other patients, or remain viable for longer time periods in the hospital environment.

Multicenter Candida auris outbreak caused by azole‐susceptible clade IV in Pernambuco, Brazil

“…The relatively high number of colonised patients and relatedness between isolates strongly suggests there was clonal transmission between patients. However, it is likely that there was more than one independent introduction of C. auris from the environment into this patient population, as we previously found a maximum number of 11 SNPs within a single C. auris outbreak over a period of 10 months in 5 patients from Kuwait 34. Moreover, the molecular clock analysis estimated the most common recent ancestor of this isolate collection around 2010, strongly suggesting there were more independent introductions from the environment in this population.…”

An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran

“…Read data were extracted from the SRA database (Supplementary Table S1). Reads were aligned and variant calling was performed as previously described [23]. All raw read data generated in this study were deposited under BioProject accession number PRJNA1002104.…”

Clinical and microbiological characteristics of a hospital outbreak of Candida auris in a referral hospital in Lima, Peru

“…fluconazole susceptible clades I and IV in Brazil). 49,50 Therefore, it is imperative to complement these data with subsequent comprehensive phylogenetic studies. Approximately 70% of patients had hospitalizations in the preceding 90 days, and some originated from dissemination in other hospitals, as well as the persistence of this organism in the environment.…”