Dataset Information

Metabolic Profiling of Candida auris, a Newly-Emerging Multi-Drug Resistant Candida Species, by GC-MS.

ABSTRACT: Candida auris, a newly-emerging Candida species, is a serious global health threat due to its multi-drug resistant pattern, difficulty to diagnose, and the high mortality associated with its invasive and bloodstream infections. Unlike C. albicans, and C. dubliniensis which can form true hyphae, C. auris grows as yeast or pseudohyphae and is capable of developing biofilms. The reasons for the inability of C. auris to form true hyphae are currently unknown. Metabolites secreted by microorganisms, including Candida, are known as important factors in controlling morphogenesis and pathogenesis. Metabolic profiling of C. auris and C. albicans cultures was performed using gas chromatography?mass spectrometry (GC?MS). Compared to C. albicans, C. auris secreted several hyphae-inhibiting metabolites, including phenylethyl, benzyl and isoamyl alcohols. Furthermore, a biofilm-forming metabolite-tyrosol-was identified. On the other hand, several other biomarkers identified from C. auris but not from C. albicans cultures may be produced by the organism to overcome the host immune system or control fungal adaptations, and hence ease its invasion and infections. The results from this study are considered as the first identification of C. auris metabolic activities as a step forward to understand its virulence mechanisms.

SUBMITTER: Semreen MH

PROVIDER: S-EPMC6384714 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Metabolic Profiling of Candida auris, a Newly-Emerging Multi-Drug Resistant Candida Species, by GC-MS.

Semreen Mohammad H MH Soliman Sameh S M SSM Saeed Balsam Q BQ Alqarihi Abdullah A Uppuluri Priya P Ibrahim Ashraf S AS

Molecules (Basel, Switzerland) 20190122 3

Candida auris, a newly-emerging Candida species, is a serious global health threat due to its multi-drug resistant pattern, difficulty to diagnose, and the high mortality associated with its invasive and bloodstream infections. Unlike C. albicans, and C. dubliniensis which can form true hyphae, C. auris grows as yeast or pseudohyphae and is capable of developing biofilms. The reasons for the inability of C. auris to form true ...[more]

PMID: 30678308

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Project description: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.IMPORTANCECandida 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.

Project description:Candida auris, a multidrug-resistant human fungal pathogen that causes outbreaks of invasive infections, emerged as four distinct geographical clades. Previous studies identified genomic and proteomic differences in nutrient utilization on comparison to Candida albicans, suggesting that certain metabolic features may contribute to C. auris emergence. Since no high-throughput clade-specific metabolic characterization has been described yet, we performed a phenotypic screening of C. auris strains from all 4 clades on 664 nutrients, 120 chemicals, and 24 stressors. We identified common and clade- or strain-specific responses, including the preferred utilization of various dipeptides as nitrogen source and the inability of the clade II isolate AR 0381 to withstand chemical stress. Further analysis of the metabolic properties of C. auris isolates showed robust growth on intermediates of the tricarboxylic acid cycle, such as citrate and succinic and malic acids. However, there was reduced or no growth on pyruvate, lactic acid, or acetate, likely due to the lack of the monocarboxylic acid transporter Jen1, which is conserved in most pathogenic Candida species. Comparison of C. auris and C. albicans transcriptomes of cells grown on alternative carbon sources and dipeptides as a nitrogen source revealed common as well as species-unique responses. C. auris induced a significant number of genes with no ortholog in C. albicans, e.g., genes similar to the nicotinic acid transporter TNA1 (alternative carbon sources) and to the oligopeptide transporter (OPT) family (dipeptides). Thus, C. auris possesses unique metabolic features which could have contributed to its emergence as a pathogen. IMPORTANCE Four main clades of the emerging, multidrug-resistant human pathogen Candida auris have been identified, and they differ in their susceptibilities to antifungals and disinfectants. Moreover, clade- and strain-specific metabolic differences have been identified, but a comprehensive overview of nutritional characteristics and resistance to various stressors is missing. Here, we performed high-throughput phenotypic characterization of C. auris on various nutrients, stressors, and chemicals and obtained transcriptomes of cells grown on selected nutrients. The generated data sets identified multiple clade- and strain-specific phenotypes and induction of C. auris-specific metabolic genes, showing unique metabolic properties. The presented work provides a large amount of information for further investigations that could explain the role of metabolism in emergence and pathogenicity of this multidrug-resistant fungus.

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

Metabolic Profiling of Candida auris, a Newly-Emerging Multi-Drug Resistant Candida Species, by GC-MS.

Publications

Metabolic Profiling of Candida auris, a Newly-Emerging Multi-Drug Resistant Candida Species, by GC-MS.

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