Candida auris, an emerging pathogenic “killer” species

On June 24, 2016 the CDC (Center for Disease Control and Prevention) published an exceptional clinical alert aimed at US healthcare facilities, warning them “to be on the lookout for C. auris in patients”.The Candida auris yeast species was first described in 2009, from a single strain isolated in a female patient (external ear discharge, hence the name “auris”) in a Japanese hospital (Satoh et al., 2009).

The phenotype, chemotaxonomic and phylogenetic characteristics (Fig1) therefore clearly suggest that this is a new species affiliated with the genusCandida (anamorph) and hence the Ascomycetes group, although the exact form is not known (teleomorph).

In particular, the sequence of genes encoding region D1/D2 of rRNA 25S of theCandida auris was very significantly different from the corresponding sequences for the type strains of species described at the time (85.7%, 83.0% and 82.4% homology only with Candida haemulonii, Candida pseudohaemulonii and Candida ruelliae, respectively) (fig. 1). Similarly, the ITS1/ITS2 region of the C. auris type strain demonstrated only 87.5%, 81.4% and 81.3% homology with the corresponding region of C. haemulonii, C. pseudohaemulonii and C.heveicola type strains.

In addition, this species was characterized by its capacity to grow at 42°C (but not at 45°C), and by its resistance to various antifungal drug classes (e.g. Azoles, 5-Flucytosine) and in the presence of 50% glucose and 10% NaCl. The cells are ovoid, (2-3 x 2-5 μm) (Fig2).

 

Epidemiology
Since this initial description, a growing number of serious urinary, respiratory and even systemic (fatal in 60-70% of cases) infections have been reported in the literature in Japan, South Korea, India, Pakistan, South Africa, Kuwait, Venezuela and England. In the latter case, an epidemic involving 40 patients in an intensive care unit persisted despite all the decontamination measures taken, patient isolation, closure of the department and other reinforced control measures. In the USA, more than 70 cases were recorded between 2016 and May 2017, following the CDC alert. These cases concerned patients of all ages, usually with well-known risk factors promoting invasive yeast infections (candidemia).
Whole-genome sequencing of strains representative of various geographic regions (outside the USA) has revealed 4 main genetic groups having emerged around the world (Pakistan-India, South Africa, Venezuela and Japan). However, within the same geographic zone, the majority of isolates were of clonal origin (same strain) (Lockart et al. 2017).

 

Pathogenicity factors
In addition to the capacity of yeasts of this species to grow at 42°C, multi-resistance (to two or more antifungal drugs) has been observed for almost half of the isolates. A small percentage of isolates were resistant to three antifungal drug classes (Azoles, Polyenes and Echinocandines). Although molecular data indicate that resistance to antifungal drugs appears to have emerged recently and simultaneously on 3 continents, the epidemic episodes involving the same clone suggest a capacity for spread and infection that is very different to that of conventional opportunistic pathogenic yeasts (Candida albicans, Candida glabrata, Candida krusei, Candida lusitaniae, Candida guilliermondii, Candida parapsilosis, etc.).
In addition, the persistence of strains from this species in hospital environments – particularly on surfaces despite decontamination measures (disinfectant) – has been demonstrated. Contamination between patients, without any contact, has also been demonstrated.

 

Diagnosis
It emerged that this species has been incorrectly identified using conventional methods (API systems, biochemical tests). Candida auris should be suspected when its biochemical systems have generated identification of Candida haemulonii (frequent confusion). Similarly, identifications asRhodotorula glutinis (with non-pink colony), Candida sake (API 20C), Candida catenulata (BD Phoenix); C. catenulata, C. famata, C. guilliermondii, ou C. lusitaniae Microscan) should be considered with caution. This may have contributed to the non-detection of this species in the past.

 

So how can we identify this species?
Recently, the VITEK 2 YST (software 8.01) system was updated and it now enables identification of Candida auris.
The species was not generally present in mass spectrum databases for MALDI-TOF identification systems. However, Bruker and VitekMS systems enable the use of “research” databases in which the species has been used, in order to reliably identify it compared to other Candida species in particular.
Identification methods via comparative sequencing of the D1/D2 region or the ITS region enable completely reliable identification of the species. In our databases (Eurofins IDmyk) we have the reference sequences of the representative strains from this species (type strain and others) and are able to very effectively identify this species. The CDC recommends the use of comparative sequencing to identify yeasts resistant to antifungal drugs and/or “ambiguously” identified as the above-mentioned species using biochemical or proteomic methods in the absence of a reference spectrum in databases.

 

Habitat
The natural habitat is not known.

 

Control methods
The CDC recommends the use of fungicidal disinfectants, but also sporicidal disinfectants, including those tried and tested for Clostridium for surfaces in hospital settings and laboratories.

 

Conclusion

The global emergence of this Candida auris yeast species is causing major concern, as did the emergence ofCryptococcus neoformans, Cryptococcus gattii, Candida glabrata, Candida krusei, etc. before it..

However, the latter did not accumulate as many factors favorable to epidemic spread, which is why the CDC issued its exceptional alert. It underlines our vulnerability to fungal infections and the limitations of the therapeutic weapons currently available to us. It also highlights the need to accurately identify microorganisms in general and yeasts in particular. Although yeasts are rarely a problem on a pharmaceutical industry level (frequency, occurrence, non thermotolerance, etc.), we regularly identify yeasts of various origins by comparative sequencing.
We are prepared for, and particularly alert to, the possible identification of this “killer” yeast.

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Dr. Arnaud CARLOTTI – EUROFINS IDmyk

arnaudcarlotti@eurofins.com

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Bibliography

Satoh, K., et al. “Candida auris sp. nov. a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a japanese hospital”. Microbiol. Immunol. 2009; 53: 41-44
Lockhart, S. , et al. ” Simulteneous emergence of multi-drug-resistant candia auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses”. Clin. infect. Dis. 2017; 64:134-139
Clancy, C. J. and Nguyen M. H. “Emergence of Candida auris : an international call to arms”. Clin. infect. Dis. 2017; 64:141-143
CDC. Clinical alert to US Healthcare facilities. “Global emergence of invasive infections caused by the multidrug-resistant yeast Candida auris”. June 2016. https://www.cdc.gov/ fungal/diseases/candidiasis/candida-auris-alert.html
CDC. Candida auris “Interim recommendations for healthcare facilities and laboratories”. https://www.cdc.gov/fungal/diseases/candidiasis/recommendations.html