Draft genome of a commonly misdiagnosed multidrug resistant pathogen Candida auris

Abstract

BackgroundCandida auris is a multidrug resistant, emerging agent of fungemia in humans. Its actual global distribution remains obscure as the current commercial methods of clinical diagnosis misidentify it as C. haemulonii. Here we report the first draft genome of C. auris to explore the genomic basis of virulence and unique differences that could be employed for differential diagnosis.ResultsMore than 99.5 % of the C. auris genomic reads did not align to the current whole (or draft) genome sequences of Candida albicans, Candida lusitaniae, Candida glabrata and Saccharomyces cerevisiae; thereby indicating its divergence from the active Candida clade. The genome spans around 12.49 Mb with 8527 predicted genes. Functional annotation revealed that among the sequenced Candida species, it is closest to the hemiascomycete species Clavispora lusitaniae. Comparison with the well-studied species Candida albicans showed that it shares significant virulence attributes with other pathogenic Candida species such as oligopeptide transporters, mannosyl transfersases, secreted proteases and genes involved in biofilm formation. We also identified a plethora of transporters belonging to the ABC and major facilitator superfamily along with known MDR transcription factors which explained its high tolerance to antifungal drugs.ConclusionsOur study emphasizes an urgent need for accurate fungal screening methods such as PCR and electrophoretic karyotyping to ensure proper management of fungemia. Our work highlights the potential genetic mechanisms involved in virulence and pathogenicity of an important emerging human pathogen namely C. auris. Owing to its diversity at the genomic scale; we expect the genome sequence to be a useful resource to map species specific differences that will help develop accurate diagnostic markers and better drug targets.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1863-z) contains supplementary material, which is available to authorized users.

Comparison of EUCAST and CLSI Reference Microdilution MICs of Eight Antifungal Compounds for Candida auris and Associated Tentative Epidemiological Cutoff Values

“…Isolates from South Africa and Venezuela were clonal, and all shared the same erg alteration (F126T in South Africa and Y132F in Venezuela), but the erg11 sequences from Indian isolates included the wild type, the Y132F or the K143R erg11-encoded amino acid sequences, although they were otherwise clonal. Moreover, Ben-Ami et al demonstrated enhanced ABC-type efflux activity compared to that of C. glabrata, a finding that is in keeping with the multiple ABC-and multidrug resistancetype transporter-encoding genes found in its genome and which suggests that drug efflux may also contribute to azole resistance in C. auris (8,25). In other Candida species, several azole resistance mechanisms often act in concert, which may lead to different degrees of MIC elevations, depending on the combination of mutations, expression of efflux pumps, target gene upregulation, etc.…”

Candida auris: A systematic review and meta‐analysis of current updates on an emerging multidrug‐resistant pathogen

“…The thermoresistance of C. auris that allows it to grow between 30 and 42°C, albeit slowly and weakly at 42°C (Satoh et al., ), is a unique characteristic that is unseen in other species of Candida . This characteristic can be used in the easy identification of this pathogen from other species and has been cited as a possible reason for the high survival of this pathogen in humans and its potential to survive in avian species (Borman et al., ; Chatterjee et al., ; Chowdhary et al., ; Satoh et al., ). Evidently, this thermoresistance will also enhance persistence in the host, aiding in the dissemination of this pathogen in the environment (Piedrahita et al., ; Schelenz et al., ; Welsh et al., ).…”

“…Of the six articles reporting on the use of whole genome sequencing to characterize the genome of C. auris (Chatterjee et al., ; Lockhart et al., ; Sharma, Kumar, Meis, Pandey, & Chowdhary, ; Sharma, Kumar, Pandey, Meis, & Chowdhary, ; Tsay et al., ; Vallabhaneni et al., ), only three gave detailed genome characteristics of the sequenced isolates (Chatterjee et al., ; Sharma et al., , ), which were all from India. In a detailed description of sequenced C. auris genomes, Chatterjee et al.…”

Candida auris for the Clinical Microbiology Laboratory: Not Your Grandfather's Candida Species

“…Whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analysis allow the analysis of C. auris isolates in high resolution, by characterizing genetic diversity of the 12.5 million base pairs in the genomes, which helps to differentiate even the most closely related isolates. C. auris reference genomes were assembled using two different types of whole genome sequencing systems, Illumina and PacBio, and those sequences were published and made publically available [9, 14, 15]. Using these methods and resources, phylogenetic trees that reveal population dynamics and structure were constructed, so that when coupled with the epidemiology, a better understanding of the spread of C. auris could be obtained.…”