Candida auris: Epidemiology, biology, antifungal resistance, and virulence

Abstract

First described in 2009 in Japan, the emerging multidrug-resistant fungal pathogen Candida auris is becoming a worldwide public health threat that has been attracting considerable attention due to its rapid and widespread emergence over the past decade. The reasons behind the recent emergence of this fungus remain a mystery to date. Genetic analyses indicate that this fungal pathogen emerged simultaneously in several different continents, where 5 genetically distinct clades of C. auris were isolated from distinct geographical locations. Although C. auris belongs to the CTG clade (its constituent species translate the CTG codon as serine instead of leucine, as in the standard code), C. auris is a haploid fungal species that is more closely related to the haploid and often multidrug-resistant species Candida haemulonii and Candida lusitaniae and is distantly related to the diploid and clinically common fungal pathogens Candida albicans and Candida tropicalis. Infections and outbreaks caused by C. auris in hospitals settings have been rising over the past several years. Difficulty in its identification, multidrug resistance properties, evolution of virulence factors, associated high mortality rates in patients, and long-term survival on surfaces in the environment make C. auris particularly problematic in clinical settings. Here, we review progress made over the past decade on the biological and clinical aspects of C. auris. Future efforts should be directed toward understanding the mechanistic details of its biology, epidemiology, antifungal resistance, and pathogenesis with a goal of developing novel tools and methods for the prevention, diagnosis, and treatment of C. auris infections.

Fig 1. A review of published literature on C. auris between January 2009 and June 2020.

(A) Literature published on topics pertaining to C. auris since its first identification. (B) Number of published articles in each year. Data for the months January to June were collected for the year 2020. A search of published papers between January 2009 and June 2020 was performed using PubMed and Web of Science databases. The terms “Candida auris” or “C. auris” were used as keywords for database searches. Non-related studies and studies not published in English were excluded from this analysis.

Fig 2. Countries with reported cases of C. auris infection or colonization from January 2009 to June 2020.

(A) Number of countries belonging to each continent that have reported infection or colonization with C. auris. (B) Countries with reported cases from January 2009 to June 2020. The first reported case from each country is denoted in red text. ARE, United Arab Emirates; AUS, Australia; AUT, Austria; BEL, Belgium; BGD, Bangladesh; CAN, Canada; CHE, Switzerland; CHL, Chile; CHN, China; COL, Colombia; CRI, Costa Rica; DEU, Germany; EGY, Egypt; ESP, Spain; FRA, France; GBR, United Kingdom; GRC, Greece; IND, India; IRN, Iran; ISR, Israel; ITA, Italy; JPN, Japan; KEN, Kenya; KOR, Korea (South); KWT, Kuwait; MYS, Malaysia; NLD, the Netherlands; NOR, Norway; OMN, Oman; PAK, Pakistan; PAN, Panama; POL, Poland; RUS, Russia; SAU, Saudi Arabia; SDN, Sudan; SGP, Singapore; THA, Thailand; USA, United States of America; VEN, Venezuela; ZAF, South Africa.

Fig 3. Maximum-likelihood phylogeny of the CTG and WGD clade species.

The phylogenic tree was generated using the program RAxML v7.3.2 using 50 protein sequences aligned with Mafft-homologs. The GTR model, gamma distribution, and 1,000 bootstraps were used to construct the phylogenetic relationships. Pathogenic characteristics (P), ploidy (H or D), and multidrug resistance (M) for each species are also shown. CTG, the CTG clade; Deb, Debaryomycetaceae; GTR, generalized time reversible; Met, Metschnikowiaceae; WGD, the Whole Genomic Duplication clade.

Fig 4. Five clades of C. auris.

The phylogenic tree was generated with the program RAxML v7.3.2 using SNPs. The GTR model, gamma distribution, and 1,000 bootstraps were used to construct the phylogenetic relationships. The MTL are also included for each clade. CHN, China; COL, Colombia; DEU, Germany; GBR, United Kingdom; GTR, generalized time reversible; IND, India; IRN, Iran; JPN, Japan; KOR, Korea (South); MTL, mating type loci; NLD, the Netherlands; PAK, Pakistan; RUS, Russia; SGP, Singapore; SNPs, single-nucleotide polymorphisms; USA, United States of America; VEN, Venezuela describe the country where the strain was first isolated; ZAF, South Africa.

Fig 5. Morphological transitions in C. auris.

(A) Colony and cellular morphologies of C. auris typical yeast form and filamentous-form phenotypes. Cells were grown on YPD medium. Images were adapted from [43]. (B) Known mechanisms for in vivo and in vitro phenotypic switching. Passage through the mouse mediates the switch between the typical yeast form and the filamentous competent yeast forms, whereas temperature mediates the in vitro switch between the filamentous competent yeast form and the filamentous forms. YPD, yeast extract peptone dextrose.