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Whole Genome Sequencing of Candida glabrata for Detection of Markers of Antifungal Drug Resistance
Published on: December 28, 2017
Multi-omics Signature of Candida auris, an Emerging and Multidrug-Resistant Pathogen
Daniel Zamith-Miranda1,2, Heino M Heyman3, Levi G Cleare1,2
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, USA.
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.
Insights
This study reveals significant molecular differences between Candida auris and Candida albicans, highlighting unique carbon utilization and metabolic pathways in C. auris that contribute to its drug resistance and virulence. These findings aid in combating this emerging fungal pathogen.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Genomics
Background:
- * Candida auris is an emerging multidrug-resistant fungal pathogen causing global outbreaks.
- * Its diagnosis remains challenging, potentially underestimating its spread.
- * Mechanisms of virulence and antifungal resistance in C. auris are largely unknown.
Purpose of the Study:
- * To compare the molecular profiles of two clinical Candida auris isolates with distinct drug susceptibility profiles against Candida albicans.
- * To elucidate the molecular mechanisms underlying C. auris's drug resistance and virulence.
- * To provide data for combating this rapidly emerging pathogenic yeast.
Main Methods:
- * Utilized a multi-omics approach to analyze two clinical C. auris isolates and one C. albicans reference strain.
- * Compared carbon utilization, lipid, and protein content between the species.
Main Results:
- * Both C. auris isolates showed remarkable similarity despite differing drug resistance profiles.
- * Significant differences in carbon utilization, lipid, and protein content were observed between C. auris and C. albicans.
- * These molecular distinctions suggest a multifactorial basis for C. auris's drug resistance and virulence.
Conclusions:
- * The molecular profile of C. auris significantly differs from C. albicans.
- * Understanding these omic differences is crucial for explaining C. auris's antifungal resistance and virulence.
- * The generated data will enhance strategies to combat C. auris infections.
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