Dataset Information

Metabolic profiling of Candida clinical isolates of different species and infection sources.

ABSTRACT: Candida species are the most common cause of opportunistic fungal infections. Rapid identification and novel approaches for the characterization of these fungi are of great interest to improve the diagnosis and the knowledge about their pathogenic properties. This study aimed to characterize clinical isolates of Candida spp. by proteomics (MALDI-TOF MS) and metabolomics (¹H-NMR), and to correlate their metabolic profiles with Candida species, source of infection and different virulence associated parameters. In particular, 49 Candida strains from different sources (blood, n = 15; vagina, n = 18; respiratory tract, n = 16), belonging mainly to C. albicans complex (61%), C. glabrata (20%) and C. parapsilosis (12%) species were used. Several extracellular and intracellular metabolites showed significantly different concentrations among isolates recovered from different sources of infection, as well as among different Candida species. These metabolites were mainly related to the glycolysis or gluconeogenesis, tricarboxylic acid cycle, nucleic acid synthesis and amino acid and lipid metabolism. Moreover, we found specific metabolic fingerprints associated with the ability to form biofilm, the antifungal resistance (i.e. caspofungin and fluconazole) and the production of secreted aspartyl proteinase. In conclusion, ¹H-NMR-based metabolomics can be useful to deepen Candida spp. virulence and pathogenicity properties.

SUBMITTER: Oliver JC

PROVIDER: S-EPMC7541501 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Metabolic profiling of Candida clinical isolates of different species and infection sources.

Oliver Josidel Conceição JC Laghi Luca L Parolin Carola C Foschi Claudio C Marangoni Antonella A Liberatore Andrea A Dias Amanda Latercia Tranches ALT Cricca Monica M Vitali Beatrice B

Scientific reports 20201007 1

Candida species are the most common cause of opportunistic fungal infections. Rapid identification and novel approaches for the characterization of these fungi are of great interest to improve the diagnosis and the knowledge about their pathogenic properties. This study aimed to characterize clinical isolates of Candida spp. by proteomics (MALDI-TOF MS) and metabolomics (<sup>1</sup>H-NMR), and to correlate their metabolic profiles with Candida species, source of infection and different virulenc ...[more]

PMID: 33028931

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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.

Dataset Information

Metabolic profiling of Candida clinical isolates of different species and infection sources.

Publications

Metabolic profiling of Candida clinical isolates of different species and infection sources.

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