ClaID: a Rapid Method of Clade-Level Identification of the Multidrug Resistant Human Fungal Pathogen Candida auris

Narayanan, Aswathy; Selvakumar, Pavitra; Siddharthan, Rahul; Sanyal, Kaustuv

doi:10.1128/spectrum.00634-22

Cited by 18 publications

(17 citation statements)

References 40 publications

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“…Accordingly, efforts have been made to refine genome-mapping criteria to save time and cut down costs. Advanced studies have recently succeeded in locating unique DNA sequence junctions that map clade-specific regions, a procedure greatly reducing the time necessary to locate the four major clades of C. auris [ 15 ]. Regarding proteomics, up-to-date MALDI-TOF databases are now available, which include C. auris strains from all four phylogenetic clades.…”

Section: Introductionmentioning

confidence: 99%

Raman Metabolomics of Candida auris Clades: Profiling and Barcode Identification

Pezzotti

Kobara

Nakaya

et al. 2022

IJMS

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This study targets on-site/real-time taxonomic identification and metabolic profiling of seven different Candida auris clades/subclades by means of Raman spectroscopy and imaging. Representative Raman spectra from different Candida auris samples were systematically deconvoluted by means of a customized machine-learning algorithm linked to a Raman database in order to decode structural differences at the molecular scale. Raman analyses of metabolites revealed clear differences in cell walls and membrane structure among clades/subclades. Such differences are key in maintaining the integrity and physical strength of the cell walls in the dynamic response to external stress and drugs. It was found that Candida cells use the glucan structure of the extracellular matrix, the degree of α-chitin crystallinity, and the concentration of hydrogen bonds between its antiparallel chains to tailor cell walls’ flexibility. Besides being an effective ploy in survivorship by providing stiff shields in the α–1,3–glucan polymorph, the α–1,3–glycosidic linkages are also water-insoluble, thus forming a rigid and hydrophobic scaffold surrounded by a matrix of pliable and hydrated β–glucans. Raman analysis revealed a variety of strategies by different clades to balance stiffness, hydrophobicity, and impermeability in their cell walls. The selected strategies lead to differences in resistance toward specific environmental stresses of cationic/osmotic, oxidative, and nitrosative origins. A statistical validation based on principal componendist analysis was found only partially capable of distinguishing among Raman spectra of clades and subclades. Raman barcoding based on an algorithm converting spectrally deconvoluted Raman sub-bands into barcodes allowed for circumventing any speciation deficiency. Empowered by barcoding bioinformatics, Raman analyses, which are fast and require no sample preparation, allow on-site speciation and real-time selection of appropriate treatments.

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Section: Introductionmentioning

confidence: 99%

Raman Metabolomics of Candida auris Clades: Profiling and Barcode Identification

Pezzotti

Kobara

Nakaya

et al. 2022

IJMS

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“…P2428 was isolated from a diabetic patient’s pus in India and was initially expected to be a clade I isolate owing to the area of its isolation. Strikingly, analysis of P2428 using clade-specific primers (20) yielded amplicons only with clade-II primers, suggesting that P2428 is a clade II isolate. The raw reads from Illumina sequencing of P2428 were then mapped to the GenBank assemblies GCA_002759435.1 (clade I, strain B11205), GCA_003013715.1 (clade II, strain B11220), GCA_016772215.1 (clade III, strain B12037), GCA_008275145.1 (clade IV, strain B11245), and GCA_016809505.1 (clade V, strain IFRC2087).…”

Section: Resultsmentioning

confidence: 99%

“…The clade-specific primers reported previously were used to identify the clade-status of the isolates (20). The whole genome data was also compared with the available GenBank assemblies of strains belonging to different clades.…”

Section: Methodsmentioning

confidence: 99%

Microevolution of clade II isolates ofCandida aurishighlights multifaceted intra-clade heterogeneity in acquiring resistance towards amphotericin B

Chauhan,

Kumar,

Kumar

et al. 2023

Preprint

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Candida aurisexhibits high-level resistance to amphotericin B (AmB). Mechanisms such as ergosterol biosynthesis malfunction, oxidative damage mismanagement, and increased drug efflux contribute to AmB resistance inC. auris. In this study, we experimentally evolved two East Asian drug-susceptible clade II isolates ofC. auris(P2428 and CBS10913T) isolated from different geographical locations to develop resistance against AmB. We analysed alterations in karyotype, genome sequence, and gene expression profiles to uncover the mechanisms driving AmB resistance. The independently evolved clade II adaptors displayed up to 4-16-fold higher MIC50, as compared to the parental cells.AOX2(alternative oxidase) and the cell wall integrity pathway have been identified as critical in the development of AmB resistance. However, we noted certain intra-clade heterogeneity in the associated mechanisms. While in P2428 adaptors (P-lines), the ergosterol and sphingolipid pathways appear to play a crucial role, this was not the case for CBS10913Tadaptors (A-lines), which acquired resistance independent of lipid-associated changes. The transcriptomic, WGS, and phenotypic analyses also confirm that the evolved AmB-resistant isolates follow distinct trajectories for adaptation, Furthermore, unlike the fluconazole-resistant isolates, as reported previously, changes in ploidy do not seem to contribute to the differential mechanisms of AmB resistance. Overall, this study not only provides insights into the mechanisms and pathways involved in AmB resistance but also highlights intra-clade-heterogeneity that exists within clade II ofC. auris.ImportanceCandida aurisdemonstrates significant resistance to amphotericin B (AmB) that stems from factors like alteration of ergosterol biosynthesis, perturbation of the oxidative damage response, etc. A comprehensive understanding of underlying mechanisms can be studied in a holistic manner by subjecting resistant as well as susceptible clinical isolates to a comparative genome-level analysis. An alternate and more dynamic approach is to expose susceptible isolates to a certain concentration of drug which is not lethal but can trigger the resistance mechanisms. In the present study, we evolvedC. auristowards AmB and observed novel and differential mechanisms of resistance development, in two different isolates despite belonging to the same clade. This study provides insights into the intra-clade heterogeneous behavior ofC. auristowards AmB.

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“…The raw reads as well as the resulted consensus sequences for each of the 16 sequenced strains, were further subject of clade classification, by mapping them onto clade specific sequences (CSS), as previously described by others [ 11 , 12 ]. The CSSs were downloaded from the NCBI database.…”

Section: Methodsmentioning

confidence: 99%

First report of Candida auris in Romania: clinical and molecular aspects

Stanciu,

Florea,

Surleac

et al. 2023

Antimicrob Resist Infect Control

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The emerging opportunistic fungal pathogen Candida auris raises significant concerns for public health due to its outbreak potential, the associated high mortality, increased resistance to antifungals, challenging identification to species level, since commonly used diagnostic methods can confuse this fungus with other Candida spp. The present outbreak report describes probably some of the first Candida auris cases in Romania, providing clinical and epidemiological data, and also whole genome sequencing data. The cases were identified in three hospitals in Bucharest during the first eight months of 2022.

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ClaID: a Rapid Method of Clade-Level Identification of the Multidrug Resistant Human Fungal Pathogen Candida auris

Abstract: C. auris was first isolated in Japan in 2009 as an antifungal drug-susceptible pathogen causing localized infections. Within a decade, it simultaneously evolved in different parts of the world as distinct clades exhibiting resistance to antifungal drugs at varying levels.

Cited by 18 publications

References 40 publications

Raman Metabolomics of Candida auris Clades: Profiling and Barcode Identification

Raman Metabolomics of Candida auris Clades: Profiling and Barcode Identification

Microevolution of clade II isolates ofCandida aurishighlights multifaceted intra-clade heterogeneity in acquiring resistance towards amphotericin B

First report of Candida auris in Romania: clinical and molecular aspects

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