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Multi-omics Signature of Candida auris, an Emerging and Multidrug-Resistant Pathogen.

ABSTRACT: Candida auris is a recently described pathogenic fungus that is causing invasive outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-resistant strains that have been isolated in distinct sites across the globe. The fact that its diagnosis is still problematic suggests that the spreading of the pathogen remains underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance employed by this new species are largely unknown. In the present work, we compared two clinical isolates of C. auris with distinct drug susceptibility profiles and a Candida albicans reference strain using a multi-omics approach. Our results show that, despite the distinct drug resistance profile, both C. auris isolates appear to be very similar, albeit with a few notable differences. However, compared to C. albicans both C. auris isolates have major differences regarding their carbon utilization and downstream lipid and protein content, suggesting a multifactorial mechanism of drug resistance. The molecular profile displayed by C. auris helps to explain the antifungal resistance and virulence phenotypes of this new emerging pathogen.IMPORTANCE Candida auris was first described in Japan in 2009 and has now been the cause of significant outbreaks across the globe. The high number of isolates that are resistant to one or more antifungals, as well as the high mortality rates from patients with bloodstream infections, has attracted the attention of the medical mycology, infectious disease, and public health communities to this pathogenic fungus. In the current work, we performed a broad multi-omics approach on two clinical isolates isolated in New York, the most affected area in the United States and found that the omic profile of C. auris differs significantly from C. albicans In addition to our insights into C. auris carbon utilization and lipid and protein content, we believe that the availability of these data will enhance our ability to combat this rapidly emerging pathogenic yeast.

SUBMITTER: Zamith-Miranda D

PROVIDER: S-EPMC6561322 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Multi-omics Signature of <i>Candida auris</i>, an Emerging and Multidrug-Resistant Pathogen.

Zamith-Miranda Daniel D Heyman Heino M HM Cleare Levi G LG Couvillion Sneha P SP Clair Geremy C GC Bredeweg Erin L EL Gacser Attila A Nimrichter Leonardo L Nakayasu Ernesto S ES Nosanchuk Joshua D JD

mSystems 20190611 4

<i>Candida auris</i> is a recently described pathogenic fungus that is causing invasive outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-resistant strains that have been isolated in distinct sites across the globe. The fact that its diagnosis is still problematic suggests that the spreading of the pathogen remains underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance employed by this new species are largely unknown. In t ...[more]

PMID: 31186339

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Project description:From 2009, Candida auris has emerged as a multidrug-resistant ascomycete yeast pathogen with the capacity for easy transmission between patients and hospitals, as well as persistence on environmental surfaces. Its association with high mortalities, breakthrough and persistent candidaemia, inconsistencies in susceptibility testing results, misidentification by available commercial identification systems and treatment failure, complicates its management and detection. Within the last nine years, C. auris has been increasingly reported from far-Eastern Asia, the Middle East, Africa, Europe, South and North America with substantial fatalities and misidentification. Herein, I provide a systematic and thorough review of this emerging pathogen. Meta-analysis showed that at least 742 C. auris isolates have been reported in 16 countries, with most of these being from India (?243), USA (?232) and UK (?103) (p-value = .0355) within 2013-2017. Most isolates were from males (64.76%) (p-value = .0329) and blood (67.48%) (p-value < .0001), with substantial crude mortality (29.75%) (p-value = .0488). Affected patients presented with other comorbidities: diabetes (?52), sepsis (?48), lung diseases (?39), kidney diseases (?32) etc. (p-value < .0001). Resistance to fluconazole (44.29%), amphotericin B (15.46%), voriconazole (12.67%), caspofungin (3.48%) etc. were common (p-value = .0059). Commonly used diagnostic tools included PCR (30.38%), Bruker MALDI-TOF MS (14.00%), Vitek 2 YST ID (11.93%), AFLP (11.55%) and WGS (10.04%) (p-value = .002). Multidrug resistance, high attributable mortality and persistence are associated with C. auris infections. Two novel drugs, SCY-078 and VT-1598, are currently in the pipeline. Contact precautions, strict infection control, periodic surveillance and cleaning with chlorine-based detergents, efficient, faster and cheaper detection tools are necessary for prevention, containment and early diagnosis of C. auris infections.

Dataset Information

Multi-omics Signature of Candida auris, an Emerging and Multidrug-Resistant Pathogen.

Publications

Multi-omics Signature of <i>Candida auris</i>, an Emerging and Multidrug-Resistant Pathogen.

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