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Genomic Epidemiology of Candida auris in Qatar Reveals Hospital Transmission Dynamics and a South Asian Origin.

ABSTRACT: Candida auris is an emerging, multidrug-resistant fungal pathogen that has become a public health threat with an increasing incidence of infections worldwide. Candida auris spreads easily among patients within and between hospitals. Infections and outbreaks caused by C. auris have been reported in the Middle East region including Oman, Kuwait, Saudi Arabia, and Qatar; however, the origin of these isolates is largely unknown. Pathogen whole genome sequencing (WGS) was used to determine the epidemiology and drug resistance mutations of C. auris in Qatar. Forty-four samples isolated from patients in three hospitals and the hospital environment were sequenced by Illumina NextSeq. Core genome single nucleotide polymorphisms (SNPs) revealed that all isolates belonged to the South Asian lineage with genetic heterogeneity that suggests previous acquisition from foreign healthcare. The genetic variability among the outbreak isolates in the two hospitals (A and B) was low. Four environmental isolates clustered with the related clinical isolates, and epidemiologically linked isolates clustered together, suggesting that the ongoing transmission of C. auris could be linked to infected/colonized patients and the hospital environment. Prominent mutations Y132F and K143R in ERG11 linked to increased fluconazole resistance were detected.

SUBMITTER: Salah H

PROVIDER: S-EPMC8004815 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Genomic Epidemiology of Candida auris in Qatar Reveals Hospital Transmission Dynamics and a South Asian Origin.

Salah Husam H Sundararaju Sathyavathi S Dalil Lamya L Salameh Sarah S Al-Wali Walid W Tang Patrick P Ben Abid Fatma F Tsui Clement K M CKM

Journal of fungi (Basel, Switzerland) 20210323 3

Candida auris is an emerging, multidrug-resistant fungal pathogen that has become a public health threat with an increasing incidence of infections worldwide. Candida auris spreads easily among patients within and between hospitals. Infections and outbreaks caused by C. auris have been reported in the Middle East region including Oman, Kuwait, Saudi Arabia, and Qatar; however, the origin of these isolates is largely unknown. Pathogen whole genome sequencing (WGS) was used to ...[more]

PMID: 33807036

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Project description:Since 2016, in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster (N = 166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these, 85% (N = 22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N = 38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates. This work describes molecular mechanisms associated with C. auris antifungal resistance in Colombia. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia.ImportanceCandida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread.

Project description:Genomic analyses are widely applied to epidemiological, population genetic and experimental studies of pathogenic fungi. A wide range of methods are employed to carry out these analyses, typically without including controls that gauge the accuracy of variant prediction. The importance of tracking outbreaks at a global scale has raised the urgency of establishing high-accuracy pipelines that generate consistent results between research groups. To evaluate currently employed methods for whole-genome variant detection and elaborate best practices for fungal pathogens, we compared how 14 independent variant calling pipelines performed across 35 Candida auris isolates from 4 distinct clades and evaluated the performance of variant calling, single-nucleotide polymorphism (SNP) counts and phylogenetic inference results. Although these pipelines used different variant callers and filtering criteria, we found high overall agreement of SNPs from each pipeline. This concordance correlated with site quality, as SNPs discovered by a few pipelines tended to show lower mapping quality scores and depth of coverage than those recovered by all pipelines. We observed that the major differences between pipelines were due to variation in read trimming strategies, SNP calling methods and parameters, and downstream filtration criteria. We calculated specificity and sensitivity for each pipeline by aligning three isolates with chromosomal level assemblies and found that the GATK-based pipelines were well balanced between these metrics. Selection of trimming methods had a greater impact on SAMtools-based pipelines than those using GATK. Phylogenetic trees inferred by each pipeline showed high consistency at the clade level, but there was more variability between isolates from a single outbreak, with pipelines that used more stringent cutoffs having lower resolution. This project generated two truth datasets useful for routine benchmarking of C. auris variant calling, a consensus VCF of genotypes discovered by 10 or more pipelines across these 35 diverse isolates and variants for 2 samples identified from whole-genome alignments. This study provides a foundation for evaluating SNP calling pipelines and developing best practices for future fungal genomic studies.

Dataset Information

Genomic Epidemiology of Candida auris in Qatar Reveals Hospital Transmission Dynamics and a South Asian Origin.

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Genomic Epidemiology of <i>Candida auris</i> in Qatar Reveals Hospital Transmission Dynamics and a South Asian Origin.

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