Genomic Characterizations of Clade III Lineage of Candida auris, California, USA.
Ontology highlight
ABSTRACT:
SUBMITTER: Price TK
PROVIDER: S-EPMC8007294 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Candida auris is an invasive and multidrug-resistant ascomycetous yeast that is under global surveillance. All clinical cases of C. auris infection diagnosed from 1997 to 2019 in Japan were non-invasive and sporadic otitis media cases. In the present study, we performed whole-genome sequencing of seven C. auris strains isolated from patients with otitis media in Japan, all of which belonged to clade II. Comparative genome analysis using the high-quality draft genome sequences JCM 15448T revealed that single nucleotide variations (SNVs), clade-specific accessory genes, and copy number variations (CNVs) were identified in each C. auris clade. A total of 61 genes involved in cell wall and stress response-related functions was absent in clade II, and the pattern of conserved CNVs in each clade was more stable in clade II than in other clades. Our data suggest that the genomic structural diversity is stable in C. auris isolated from each biogeographic location, and Japanese strains isolated from patients with otitis media might belong to an ancestral type of C. auris. One Japanese strain, TWCC 58362, with reduced susceptibility to fluconazole, exhibited no mutation in ergosterol biosynthesis-related genes (ERG). However, TWCC 58362-specific variations, including SNVs, indels, and CNVs were detected, suggesting that gene duplication events in C. auris might contribute to antifungal drug resistance. Taken together, we demonstrated that genomic structural variations in C. auris could correlate to geographical dissemination, epidemiology, lesions in the host, and antifungal resistance.
| S-EPMC6785063 | biostudies-literature
Project description:Candida auris is a pathogen of considerable public health importance. It was first reported in 2009. Five clades, determined by genomic analysis and named by the distinct regions where they were initially identified, have been defined. We previously completed a draft genome sequence of an African clade (clade III) strain cultured from the urine of a patient hospitalized in the greater Houston metropolitan region (strain LOM). Although initially uncommon, reports of the African clade in the United States have grown to include a recent cluster in California. Here, we describe a second human C. auris infection in the Houston area. Whole-genome sequence analysis demonstrated the Houston patient isolates to be clonally related to one another but distantly related to other African clade organisms recovered in the United States or elsewhere. Infections in these patients were present on admission to the hospital and occurred several months apart. Taken together, the data demonstrate the emergence and persistence of a clonal C. auris population and highlights the importance of routine high-resolution genomic surveillance of emerging human pathogens in the clinical laboratory.
| S-EPMC7315038 | biostudies-literature
Project description:Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country.
| S-EPMC6711235 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-03-30 | GSE223412 | GEO
Project description:Candida auris is an emerging fungal pathogen of rising concern due to global spread, the ability to cause healthcare-associated outbreaks, and antifungal resistance. Genomic analyses revealed that early contemporaneously detected cases of C. auris were geographically stratified into four major clades. While Clades I, III, and IV are responsible for ongoing outbreaks of invasive and multidrug-resistant infections, Clade II, also termed the East Asian clade, consists primarily of cases of ear infection, is often susceptible to all antifungal drugs, and has not been associated with outbreaks. Here, we generate chromosome-level assemblies of twelve isolates representing the phylogenetic breadth of these four clades and the only isolate described to date from Clade V. This Clade V genome is highly syntenic with those of Clades I, III, and IV, although the sequence is highly divergent from the other clades. Clade II genomes appear highly rearranged, with translocations occurring near GC-poor regions, and large subtelomeric deletions in most chromosomes, resulting in a substantially different karyotype. Rearrangements and deletion lengths vary across Clade II isolates, including two from a single patient, supporting ongoing genome instability. Deleted subtelomeric regions are enriched in Hyr/Iff-like cell-surface proteins, novel candidate cell wall proteins, and an ALS-like adhesin. Cell wall proteins from these families and other drug-related genes show clade-specific signatures of selection in Clades I, III, and IV. Subtelomeric dynamics and the conservation of cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggest an explanation for the different phenotypes observed between clades.
| S-EPMC8128392 | biostudies-literature
Project description:Candida auris is an emerging fungal pathogen that is typically resistant to fluconazole and is known to cause healthcare-associated outbreaks. We retrospectively reviewed 28 patients who had >1 positive culture for C. auris within a multisite health system in Illinois, USA, during May 2018-April 2019. Twelve of these patients were treated as inpatients for C. auris infections; 10 (83%) met criteria for clinical success, defined as absence of all-cause mortality, C. auris recurrence, and infection-related readmission at 30 days from the first positive culture. The other 2 patients (17%) died within 30 days. Most patients (92%) were empirically treated with micafungin. Four (14%) of 28 total isolates were resistant to fluconazole, 1 (3.6%) was resistant to amphotericin B, and 1 (3.6%) was resistant to echinocandins. Our findings describe low rates of antifungal resistance and favorable clinical outcomes for most C. auris patients.
| S-EPMC7181927 | biostudies-literature
Project description:BackgroundTransmission of multidrug-resistant Candida auris infection has been reported in the USA. To better understand its emergence and transmission dynamics and to guide clinical and public health responses, we did a molecular epidemiological investigation of C auris cases in the USA.MethodsIn this molecular epidemiological survey, we used whole-genome sequencing to assess the genetic similarity between isolates collected from patients in ten US states (California, Connecticut, Florida, Illinois, Indiana, Maryland, Massachusetts, New Jersey, New York, and Oklahoma) and those identified in several other countries (Colombia, India, Japan, Pakistan, South Africa, South Korea, and Venezuela). We worked with state health departments, who provided us with isolates for sequencing. These isolates of C auris were collected during the normal course of clinical care (clinical cases) or as part of contact investigations or point prevalence surveys (screening cases). We integrated data from standardised case report forms and contact investigations, including travel history and epidemiological links (ie, patients that had shared a room or ward with a patient with C auris). Genetic diversity of C auris within a patient, a facility, and a state were evaluated by pairwise differences in single-nucleotide polymorphisms (SNPs).FindingsFrom May 11, 2013, to Aug 31, 2017, isolates that corresponded to 133 cases (73 clinical cases and 60 screening cases) were collected. Of 73 clinical cases, 66 (90%) cases involved isolates related to south Asian isolates, five (7%) cases were related to South American isolates, one (1%) case to African isolates, and one (1%) case to east Asian isolates. Most (60 [82%]) clinical cases were identified in New York and New Jersey; these isolates, although related to south Asian isolates, were genetically distinct. Genomic data corroborated five (7%) clinical cases in which patients probably acquired C auris through health-care exposures abroad. Among clinical and screening cases, the genetic diversity of C auris isolates within a person was similar to that within a facility during an outbreak (median SNP difference three SNPs, range 0-12).InterpretationIsolates of C auris in the USA were genetically related to those from four global regions, suggesting that C auris was introduced into the USA several times. The five travel-related cases are examples of how introductions can occur. Genetic diversity among isolates from the same patients, health-care facilities, and states indicates that there is local and ongoing transmission.FundingUS Centers for Disease Control and Prevention.
| S-EPMC6556114 | biostudies-literature
Project description:Candida auris was first described in 2009, and it has since caused nosocomial outbreaks, invasive infections, and fungaemia across at least 19 countries on five continents. An outbreak of C. auris occurred in a specialized cardiothoracic London hospital between April 2015 and November 2016, which to date has been the largest outbreak in the UK, involving a total of 72 patients. To understand the genetic epidemiology of C. auris infection both within this hospital and within a global context, we sequenced the outbreak isolate genomes using Oxford Nanopore Technologies and Illumina platforms to detect antifungal resistance alleles and reannotate the C. auris genome. Phylogenomic analysis placed the UK outbreak in the India/Pakistan clade, demonstrating an Asian origin; the outbreak showed similar genetic diversity to that of the entire clade, and limited local spatiotemporal clustering was observed. One isolate displayed resistance to both echinocandins and 5-flucytosine; the former was associated with a serine to tyrosine amino acid substitution in the gene FKS1, and the latter was associated with a phenylalanine to isoleucine substitution in the gene FUR1. These mutations add to a growing body of research on multiple antifungal drug targets in this organism. Multiple differential episodic selection of antifungal resistant genotypes has occurred within a genetically heterogenous population across this outbreak, creating a resilient pathogen and making it difficult to define local-scale patterns of transmission and implement outbreak control measures.
| S-EPMC5874254 | biostudies-literature
Project description:Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360?years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38?years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.
| S-EPMC7188998 | biostudies-literature
Project description:In South Africa, Candida auris was the third most common cause of candidemia in 2016-2017. We performed single nucleotide polymorphism (SNP) genome-wide analysis of 115 C. auris isolates collected between 2009 and 2018 from national laboratory-based surveillance, an environmental survey at four hospitals and a colonization study during a neonatal unit outbreak. The first known South African C. auris strain from 2009 clustered in clade IV. Overall, 98 strains clustered within clade III (85%), 14 within clade I (12%) and three within clade IV (3%). All environmental and colonizing strains clustered in clade III. We also identified known clade-specific resistance mutations in the ERG11 and FKS1 genes. Identification of clade I strains between 2016 and 2018 suggests introductions from South Asia followed by local transmission. SNP analysis characterized most C. auris strains into clade III, the clade first reported from South Africa, but the presence of clades I and IV strains also suggest early introductions from other regions.
| S-EPMC8253216 | biostudies-literature