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Colonisation and Transmission Dynamics of Candida auris among Chronic Respiratory Diseases Patients Hospitalised in a Chest Hospital, Delhi, India: A Comparative Analysis of Whole Genome Sequencing and Microsatellite Typing.

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TLDR
In this paper, the authors investigated the relationships among C. auris isolates from patients with chronic respiratory diseases admitted in a chest hospital and from their fomites, using whole-genome sequencing (WGS) and multilocus microsatellite genotyping.
Abstract
Candida auris is a nosocomial pathogen responsible for an expanding global public health threat. This ascomycete yeast has been frequently isolated from hospital environments, representing a significant reservoir for transmission in healthcare settings. Here, we investigated the relationships among C. auris isolates from patients with chronic respiratory diseases admitted in a chest hospital and from their fomites, using whole-genome sequencing (WGS) and multilocus microsatellite genotyping. Overall, 37.5% (n = 12/32) patients developed colonisation by C. auris including 9.3% of the screened patients that were colonised at the time of admission and 75% remained colonised till discharge. Furthermore, 10% of fomite samples contained C. auris in rooms about 8.5 days after C. auris colonised patients were admitted. WGS and microsatellite typing revealed that multiple strains contaminated the fomites and colonised different body sites of patients. Notably, 37% of C. auris isolates were resistant to amphotericin B and a novel amino acid substitution, G145D in ERG2 gene, was detected in all amphotericin B resistant isolates. In addition, 55% of C. auris isolates had two copies of the MDR1 gene. Our results suggest significant genetic and ecological diversities of C. auris in healthcare setting. The WGS and microsatellite genotyping methods provided complementary results in genotype identification.

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Candida auris: Epidemiology, Diagnosis, Pathogenesis, Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in Healthcare Facilities

TL;DR: In this article, the authors highlight the lessons learned from recent studies on the epidemiology, diagnosis, pathogenesis, susceptibility, and molecular basis of resistance to antifungal drugs and infection control measures to combat the spread of C. auris infections in healthcare facilities.
Journal ArticleDOI

Genome-Wide Analysis of Experimentally Evolved Candida auris Reveals Multiple Novel Mechanisms of Multidrug Resistance.

Abstract: Candida auris is globally recognized as an opportunistic fungal pathogen of high concern, due to its extensive multidrug resistance (MDR) Still, molecular mechanisms of MDR are largely unexplored This is the first account of genome-wide evolution of MDR in C auris obtained through serial in vitro exposure to azoles, polyenes, and echinocandins We show the stepwise accumulation of copy number variations and novel mutations in genes both known and unknown in antifungal drug resistance Echinocandin resistance was accompanied by a codon deletion in FKS1 hot spot 1 and a substitution in FKS1 “novel” hot spot 3 Mutations in ERG3 and CIS2 further increased the echinocandin MIC Decreased azole susceptibility was linked to a mutation in transcription factor TAC1b and overexpression of the drug efflux pump Cdr1, a segmental duplication of chromosome 1 containing ERG11, and a whole chromosome 5 duplication, which contains TAC1b The latter was associated with increased expression of ERG11, TAC1b, and CDR2 but not CDR1 The simultaneous emergence of nonsense mutations in ERG3 and ERG11 was shown to decrease amphotericin B susceptibility, accompanied with fluconazole cross-resistance A mutation in MEC3, a gene mainly known for its role in DNA damage homeostasis, further increased the polyene MIC Overall, this study shows the alarming potential for and diversity of MDR development in C auris, even in a clade until now not associated with MDR (clade II), stressing its clinical importance and the urge for future research IMPORTANCECandida auris is a recently discovered human fungal pathogen and has shown an alarming potential for developing multi- and pan-resistance toward all classes of antifungals most commonly used in the clinic Currently, C auris has been globally recognized as a nosocomial pathogen of high concern due to this evolutionary potential So far, this is the first study in which the stepwise progression of multidrug resistance (MDR) in C auris is monitored in vitro Multiple novel mutations in known resistance genes and genes previously not or vaguely associated with drug resistance reveal rapid MDR evolution in a C auris clade II isolate Additionally, this study shows that in vitro experimental evolution can be a powerful tool to discover new drug resistance mechanisms, although it has its limitations
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Molecular Epidemiological Investigation of a Nosocomial Cluster of C. auris : Evidence of Recent Emergence in Italy and Ease of Transmission during the COVID-19 Pandemic.

TL;DR: In this paper, the authors used whole-genome sequencing (WGS) and antifungal susceptibility testing (AST) to identify C. auris in Italy and found that most transmissions were associated with a ward converted to a COVID-19dedicated ICU during the pandemic.
Journal ArticleDOI

What Do We Know about Candida auris ? State of the Art, Knowledge Gaps, and Future Directions.

TL;DR: A review summarises the current evidence on C. auris since its first description, from virulence to treatment and outbreak control, and highlights the knowledge gaps and future directions for research efforts.
Journal ArticleDOI

Candida auris on Apples: Diversity and Clinical Significance

TL;DR: The findings suggest that C. auris in the natural ecosystem may come in contact with agriculture fungicides and that stored fruits could be a significant niche for the selection of azole resistance in C. Auris.
References
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TL;DR: Timmomatic is developed as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data and is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested.
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Journal ArticleDOI

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TL;DR: BEAST is a fast, flexible software architecture for Bayesian analysis of molecular sequences related by an evolutionary tree that provides models for DNA and protein sequence evolution, highly parametric coalescent analysis, relaxed clock phylogenetics, non-contemporaneous sequence data, statistical alignment and a wide range of options for prior distributions.
Journal ArticleDOI

Mathematical model for studying genetic variation in terms of restriction endonucleases

TL;DR: A mathematical model for the evolutionary change of restriction sites in mitochondrial DNA is developed and a measure called "nucleotide diversity" is proposed to express the degree of polymorphism in a population at the nucleotide level.
Posted ContentDOI

Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM

Heng Li
- 16 Mar 2013 - 
TL;DR: BWA-MEM automatically chooses between local and end-to-end alignments, supports paired-end reads and performs chimeric alignment, which is robust to sequencing errors and applicable to a wide range of sequence lengths from 70bp to a few megabases.
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