Genomic Characterizations of Clade III Lineage of Candida auris, California, USA.
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SUBMITTER: Price TK
PROVIDER: S-EPMC8007294 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
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Genomic Characterizations of Clade III Lineage of Candida auris, California, USA.
Price Travis K TK Mirasol Ruel R Ward Kevin W KW Dayo Ayrton J AJ Hilt Evann E EE Chandrasekaran Sukantha S Garner Omai B OB de St Maurice Annabelle A Yang Shangxin S
Emerging infectious diseases 20210101 4
Candida auris is an emerging multidrug-resistant yeast. We describe an ongoing C. auris outbreak that began in October 2019 in Los Angeles, California, USA. We used genomic analysis to determine that isolates from 5 of 6 patients belonged to clade III; 4 isolates were closely related. ...[more]
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Project description:BackgroundCandida auris is an emerging fungal pathogen causing outbreaks in healthcare facilities. Five distinctive genomic clades exhibit clade-unique characteristics, highlighting the importance of real-time genomic surveillance and incorporating genotypic information to inform infection prevention practices and treatment algorithms.MethodsBoth active and passive surveillance were used to screen hospitalized patients. C. auris polymerase chain reaction (PCR) assay on inguinal-axillary swabs was performed on high-risk patients upon admission. All clinical yeast isolates were identified to the species level. C. auris isolates were characterized by both phenotypic antifungal susceptibility tests and whole-genome sequencing.ResultsFrom late 2019 to early 2022, we identified 45 patients with C. auris. Most had a tracheostomy or were from a facility with a known outbreak. Moreover, 7 patients (15%) were only identified through passive surveillance. Also, 8 (18%) of the patients had a history of severe COVID-19. The overall mortality was 18%. Invasive C. auris infections were identified in 13 patients (29%), 9 (69%) of whom had bloodstream infections. Patients with invasive infection were more likely to have a central line. All C. auris isolates were resistant to fluconazole but susceptible to echinocandins. Genomic analysis showed that 1 dominant clade-III lineage is circulating in Los Angeles, with very limited intrahost and interhost genetic diversity.ConclusionsWe have demonstrated that a robust C. auris surveillance program can be established using both active and passive surveillance, with multidisciplinary efforts involving the microbiology laboratory and the hospital epidemiology team. In Los Angeles County, C. auris strains are highly related and echinocandins should be used for empiric therapy.
| S-EPMC10369217 | biostudies-literature
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:The rapid increase in infections caused by the emerging fungal pathogen Candida auris is of global concern, and understanding its expansion is a priority. The phylogenetic diversity of the yeast is clustered in five major clades, among which clade III is particularly relevant, as most of its strains exhibit resistance to fluconazole, reducing the therapeutic alternatives and provoking outbreaks that are difficult to control. In this study, we have investigated the phylogenetic structure of clade III by analyzing a global collection of 566 genomes. We have identified three subgroups within clade III, among which two are genetically most closely related. Moreover, we have estimated the evolutionary rate of clade III to be 2.25e-7 s/s/y (2.87 changes per year). We found that one of these subgroups shows intrinsic resistance to fluconazole and is responsible for the majority of cases within this clade globally. We inferred that this subgroup may have originated around December 2010 (95% High Probability Density (HPD): April 2010-June 2011), and since then it has spread across continents, generating multiple large outbreaks, each with a unique pattern of transmission and dissemination. These results highlight the remarkable ability of the pathogen to adapt to its environment and its rapid global spread, underscoring the urgent need to address this epidemiological challenge effectively.IMPORTANCEThe number of cases affected by Candida auris has increased worryingly worldwide. Among the currently recognized clades, clade III has the highest proportion of fluconazole-resistant cases and is spreading very rapidly, causing large nosocomial outbreaks across the globe. By analyzing complete fungal genomes from around the world, we have confirmed the origin of this clade and unraveled its dispersal patterns in the early 2010s. This finding provides knowledge that may be helpful to the public health authorities for the control of the disease.
| S-EPMC11796387 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-03-30 | GSE223412 | GEO
Project description:Candida auris has emerged globally as a multidrug-resistant pathogen causing outbreaks in health care facilities. Whole genome sequencing (WGS) analysis has identified four major clades, while earlier WGS data from a single Iranian isolate suggested the existence of a potential fifth clade. Here, we confirm the existence of this fifth clade by providing WGS data of another four Iranian isolates. These clade V isolates differed less than 100 single-nucleotide polymorphisms (SNPs) between each other, while they were separated from the other clades by more than 200,000 SNPs. Two of these isolates were resistant to fluconazole and were found to harbour mutations in the TAC1b and ERG11 genes.
| S-EPMC9586689 | biostudies-literature
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.
| S-EPMC10269459 | biostudies-literature
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, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11_Y132F mutation conferring azole resistance while FCY1_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.
| S-EPMC11218448 | biostudies-literature