scholarly journals Candida auris: A Decade of Understanding of an Enigmatic Pathogenic Yeast

2020 ◽  
Vol 6 (1) ◽  
pp. 30 ◽  
Author(s):  
Ryan Kean ◽  
Jason Brown ◽  
Dolunay Gulmez ◽  
Alicia Ware ◽  
Gordon Ramage
Keyword(s):  
Candida Auris ◽  
Pathogenic Yeast ◽  
Clinical Concern

Candida auris is an enigmatic yeast that continues to stimulate interest within the mycology community due its rapid and simultaneous emergence of distinct clades. In the last decade, almost 400 manuscripts have contributed to our understanding of this pathogenic yeast. With dynamic epidemiology, elevated resistance levels and an indication of conserved and unique pathogenic traits, it is unsurprising that it continues to cause clinical concern. This mini-review aims to summarise some of the key attributes of this remarkable pathogenic yeast.

scholarly journals Diagnostic Allele-Specific PCR for the Identification of Candida auris Clades

2021 ◽  
Vol 7 (9) ◽  
pp. 754
Author(s):  
Hans Carolus ◽  
Stef Jacobs ◽  
Celia Lobo Romero ◽  
Quinten Deparis ◽  
Christina A. Cuomo ◽  
...  
Keyword(s):  
Low Income ◽  
Clinical Importance ◽  
Low Income Countries ◽  
Phenotypic Traits ◽  
Specific Gene ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Specific Pcr ◽  
Allele Specific ◽  
Opportunistic Pathogenic

Candida auris is an opportunistic pathogenic yeast that emerged worldwide during the past decade. This fungal pathogen poses a significant public health threat due to common multidrug resistance (MDR), alarming hospital outbreaks, and frequent misidentification. Genomic analyses have identified five distinct clades that are linked to five geographic areas of origin and characterized by differences in several phenotypic traits such as virulence and drug resistance. Typing of C. auris strains and the identification of clades can be a powerful tool in molecular epidemiology and might be of clinical importance by estimating outbreak and MDR potential. As C. auris has caused global outbreaks, including in low-income countries, typing C. auris strains quickly and inexpensively is highly valuable. We report five allele-specific polymerase chain reaction (AS-PCR) assays for the identification of C. auris and each of the five described clades of C. auris based on conserved mutations in the internal transcribed spacer (ITS) rDNA region and a clade-specific gene cluster. This PCR method provides a fast, cheap, sequencing-free diagnostic tool for the identification of C. auris, C. auris clades, and potentially, the discovery of new clades.

scholarly journals Insights into the Unique Nature of the East Asian Clade of the Emerging Pathogenic Yeast Candida auris

2019 ◽  
Vol 57 (4) ◽  
Author(s):  
Rory M. Welsh ◽  
D. Joseph Sexton ◽  
Kaitlin Forsberg ◽  
Snigdha Vallabhaneni ◽  
Anastasia Litvintseva
Keyword(s):  
Large Scale ◽  
East Asian ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Content Type ◽  
New Information ◽  
Asian Clade ◽  
Single Region ◽  
Invasive Infections ◽  
Unique Nature

ABSTRACT The emerging yeast Candida auris can be highly drug resistant, causing invasive infections, and large outbreaks. C. auris went from an unknown pathogen a decade ago to being reported in over thirty countries on six continents. C. auris consists of four discrete clades, based on where the first isolates of the clade were reported, South Asian (clade I), East Asian (clade II), African (clade III), and South American (clade IV). These clades have unique genetic and biochemical characteristics that are important to understand and inform the global response to C. auris. Clade II has been underrepresented in the literature despite being the first one discovered. In this issue of the Journal of Clinical Microbiology, Y. J. Kwon et al. (J Clin Microbiol 57:e01624-18, 2019, https://doi.org/10.1128/JCM.01624-18) describe the largest collection of clinical isolates from Clade II, which is also the longest-running span of clinical cases, 20 years, from any single region to date. Clade II appears to have a propensity for the ear that is uncharacteristic of the other clades, which typically cause invasive infections and large-scale outbreaks. This study provides new information on an understudied lineage of C. auris and has important implications for future surveillance.

scholarly journals A Zinc Cluster Transcription Factor Contributes to the Intrinsic Fluconazole Resistance of Candida auris

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Eva-Maria Mayr ◽  
Bernardo Ramírez-Zavala ◽  
Ines Krüger ◽  
Joachim Morschhäuser
Keyword(s):  
Transcription Factor ◽  
Efflux Pumps ◽  
Azole Resistance ◽  
Drug Resistant ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Fluconazole Resistance ◽  
Content Type ◽  
Zinc Cluster ◽  
Genes Encoding

ABSTRACT The recently emerged pathogenic yeast Candida auris is a major concern for human health, because it is easily transmissible, difficult to eradicate from hospitals, and highly drug resistant. Most C. auris isolates are resistant to the widely used antifungal drug fluconazole due to mutations in the target enzyme Erg11 and high activity of efflux pumps, such as Cdr1. In the well-studied, distantly related yeast Candida albicans, overexpression of drug efflux pumps also is a major mechanism of acquired fluconazole resistance and caused by gain-of-function mutations in the zinc cluster transcription factors Mrr1 and Tac1. In this study, we investigated a possible involvement of related transcription factors in efflux pump expression and fluconazole resistance of C. auris. The C. auris genome contains three genes encoding Mrr1 homologs and two genes encoding Tac1 homologs, and we generated deletion mutants lacking these genes in two fluconazole-resistant strains from clade III and clade IV. Deletion of TAC1b decreased the resistance to fluconazole and voriconazole in both strain backgrounds, demonstrating that the encoded transcription factor contributes to azole resistance in C. auris strains from different clades. CDR1 expression was not or only minimally affected in the mutants, indicating that Tac1b can confer increased azole resistance by a CDR1-independent mechanism. IMPORTANCE Candida auris is a recently emerged pathogenic yeast that within a few years after its initial description has spread all over the globe. C. auris is a major concern for human health, because it can cause life-threatening systemic infections, is easily transmissible, and is difficult to eradicate from hospital environments. Furthermore, C. auris is highly drug resistant, especially against the widely used antifungal drug fluconazole. Mutations in the drug target and high activity of efflux pumps are associated with azole resistance, but it is not known how drug resistance genes are regulated in C. auris. We have investigated the potential role of several candidate transcriptional regulators in the intrinsic fluconazole resistance of C. auris and identified a transcription factor that contributes to the high resistance to fluconazole and voriconazole of two C. auris strains from different genetic clades, thereby providing insight into the molecular basis of drug resistance of this medically important yeast.

CHROMagarTM Candida Plus: A novel chromogenic agar that permits the rapid identification of Candida auris

2020 ◽  
Author(s):  
Andrew M Borman ◽  
Mark Fraser ◽  
Elizabeth M Johnson
Keyword(s):  
Candida Species ◽  
Rapid Identification ◽  
Hospital Environment ◽  
Candida Auris ◽  
Large Hospital ◽  
Pathogenic Yeast ◽  
Isolation Medium ◽  
Wide Range ◽  
Chromogenic Agar ◽  
Environment Identification

Abstract   Candida auris is a serious nosocomial health risk, with widespread outbreaks in hospitals worldwide. Successful management of such outbreaks has depended upon intensive screening of patients to identify those that are colonized and the subsequent isolation or cohorting of affected patients to prevent onward transmission. Here we describe the evaluation of a novel chromogenic agar, CHROMagarTM Candida Plus, for the specific identification of Candida auris isolates from patient samples. Candida auris colonies on CHROMagarTM Candida Plus are pale cream with a distinctive blue halo that diffuses into the surrounding agar. Of over 50 different species of Candida and related genera that were cultured in parallel, only the vanishingly rare species Candida diddensiae gave a similar appearance. Moreover, both the rate of growth and number of colonies of C. auris recovered from swabs of pure and mixed Candida species were substantially increased on CHROMagarTM Candida Plus agar when compared with growth on the traditional mycological isolation medium, Sabouraud dextrose agar. Taken together, the present data suggest that CHROMagarTM Candida Plus agar is an excellent alternative to current conventional mycological media for the screening of patients who are potentially colonized/infected with Candida auris, can be reliably used to identify this emerging fungal pathogen, and should be tested in a clinical setting. Lay Abstract Candida auris is a novel pathogenic yeast that has been associated with large hospital outbreaks across several continents. Affected patients become colonized, predominantly on the skin, with large quantities of C. auris which they then shed into the hospital environment. Identification of C. auris is challenging using routine laboratory methods, and time consuming when patients are colonized with a mixture of different Candida species. Here we demonstrate that a novel chromogenic agar, CHROMagarTM Candida Plus, permits the rapid differentiation of C. auris from a wide range of other yeast species and is potentially ideally suited to screening of patients that are suspected of being colonized or infected with this medically important yeast.

scholarly journals Bismuth Nanoantibiotics Display Anticandidal Activity and Disrupt the Biofilm and Cell Morphology of the Emergent Pathogenic Yeast Candida auris

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 461
Author(s):  
Roberto Vazquez-Munoz ◽  
Fernando D. Lopez ◽  
Jose L. Lopez-Ribot
Keyword(s):  
Antimicrobial Activity ◽  
Cell Morphology ◽  
Multidrug Resistant ◽  
Moderate Activity ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Biofilm Growth ◽  
Healthcare Facilities ◽  
Bismuth Nanoparticles ◽  
Ic50 Values

Candida auris is an emergent multidrug-resistant pathogenic yeast, which forms biofilms resistant to antifungals, sanitizing procedures, and harsh environmental conditions. Antimicrobial nanomaterials represent an alternative to reduce the spread of pathogens—including yeasts—regardless of their drug-resistant profile. Here we have assessed the antimicrobial activity of easy-to-synthesize bismuth nanoparticles (BiNPs) against the emergent multidrug-resistant yeast Candida auris, under both planktonic and biofilm growing conditions. Additionally, we have examined the effect of these BiNPs on cell morphology and biofilm structure. Under planktonic conditions, BiNPs MIC values ranged from 1 to 4 µg mL−1 against multiple C. auris strains tested, including representatives of all different clades. Regarding the inhibition of biofilm formation, the calculated BiNPs IC50 values ranged from 5.1 to 113.1 µg mL−1. Scanning electron microscopy (SEM) observations indicated that BiNPs disrupted the C. auris cell morphology and the structure of the biofilms. In conclusion, BiNPs displayed strong antifungal activity against all strains of C. auris under planktonic conditions, but moderate activity against biofilm growth. BiNPs may potentially contribute to reducing the spread of C. auris strains at healthcare facilities, as sanitizers and future potential treatments. More research on the antimicrobial activity of BiNPs is warranted.

scholarly journals Delineation of the Direct Contribution of Candida auris ERG11 Mutations to Clinical Triazole Resistance

2021 ◽  
Author(s):  
Jeffrey M. Rybak ◽  
Cheshta Sharma ◽  
Laura A. Doorley ◽  
Katherine S. Barker ◽  
Glen E. Palmer ◽  
...  
Keyword(s):  
Health Care ◽  
Antifungal Agents ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type ◽  
Direct Contribution ◽  
Clinical Concern

Candida auris is an emerging multidrug-resistant and health care-associated pathogen of urgent clinical concern. The triazoles are the most widely prescribed antifungal agents worldwide and are commonly utilized for the treatment of invasive Candida infections.

scholarly journals In Vitro Evaluation of Antifungal Drug Combinations against Multidrug-Resistant Candida auris Isolates from New York Outbreak

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Brittany O’Brien ◽  
Sudha Chaturvedi ◽  
Vishnu Chaturvedi
Keyword(s):  
New York ◽  
Drug Combination ◽  
Multidrug Resistant ◽  
Drug Combinations ◽  
Health Care Facilities ◽  
Antifungal Drugs ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Content Type

ABSTRACT Since 2016, New York hospitals and health care facilities have faced an unprecedented outbreak of the pathogenic yeast Candida auris. We tested over 1,000 C. auris isolates from affected facilities and found high resistance to fluconazole (MIC > 256 mg/liter) and variable resistance to other antifungal drugs. Therefore, we tested if two-drug combinations are effective in vitro against multidrug-resistant C. auris. Broth microdilution antifungal combination plates were custom manufactured by TREK Diagnostic System. We used 100% inhibition endpoints for the drug combination as reported earlier for the intra- and interlaboratory agreements against Candida species. The results were derived from 12,960 readings, for 15 C. auris isolates tested against 864 two-drug antifungal combinations for nine antifungal drugs. Flucytosine (5FC) at 1.0 mg/liter potentiated the most combinations. For nine C. auris isolates resistant to amphotericin B (AMB; MIC ≥ 2.0 mg/liter), AMB-5FC (0.25/1.0 mg/liter) yielded 100% inhibition. Six C. auris isolates resistant to three echinocandins (anidulafungin [AFG], MIC ≥ 4.0 mg/liter; caspofungin [CAS], MIC ≥ 2.0 mg/liter; and micafungin [MFG], MIC ≥ 4.0 mg/liter) were 100% inhibited by AFG-5FC and CAS-5FC (0.0078/1 mg/liter) and MFG-5FC (0.12/1 mg/liter). None of the combinations were effective for C. auris 18-1 and 18-13 (fluconazole [FLC] > 256 mg/liter, 5FC > 32 mg/liter) except MFG-5FC (0.1/0.06 mg/liter). Thirteen isolates with a high voriconazole (VRC) MIC (>2 mg/liter) were 100% inhibited by the VRC-5FC (0.015/1 mg/liter). The simplified two-drug combination susceptibility test format would permit laboratories to provide clinicians and public health experts with additional data to manage multidrug-resistant C. auris.

scholarly journals Efficacy of Delayed Therapy with Fosmanogepix (APX001) in a Murine Model of Candida auris Invasive Candidiasis

2019 ◽  
Vol 63 (11) ◽  
Author(s):  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
Karen J. Shaw ◽  
Rosie Jaramillo ◽  
Hoja Patterson ◽  
...  
Keyword(s):  
Murine Model ◽  
Invasive Candidiasis ◽  
Pathogenic Fungi ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Once Daily ◽  
Content Type ◽  
Fungal Burden ◽  
Fluconazole Resistant

ABSTRACT The emerging pathogenic yeast Candida auris is associated with antifungal resistance and high mortality. The novel antifungal agent manogepix (APX001A) inhibits glycosylphosphatidylinositol-anchored protein maturation and has demonstrated activity against numerous pathogenic fungi, including C. auris. Our objective was to evaluate the in vivo efficacy of fosmanogepix, the N-phosphonooxymethyl prodrug (APX001), following delayed initiation of therapy in a murine model of C. auris invasive candidiasis. Neutropenic mice were intravenously infected with a fluconazole-resistant clinical isolate of C. auris. Twenty-four hours postinoculation, treatment began with vehicle control, fosmanogepix (104 and 130 mg/kg of body weight by intraperitoneal injection three times daily, or intraperitoneal 260 mg/kg twice daily), fluconazole (20 mg/kg by oral gavage once daily), or caspofungin (intraperitoneal 10 mg/kg once daily) and continued for 7 days. Fungal burden was assessed via colony count in the kidneys and brains on day 8 in the fungal burden arm and on day 21 as the mice became moribund in the survival arm. Significant improvements in survival were observed in each group administered fosmanogepix and caspofungin. Similarly, reductions in fungal burden were also observed in both the kidneys and brains of mice treated with the highest dose of fosmanogepix in the fungal burden arm and in each fosmanogepix group and with caspofungin in the survival arm. In contrast, no improvements in survival or reductions in fungal burden were observed in mice treated with fluconazole. These results demonstrate that fosmanogepix is effective in vivo against fluconazole-resistant C. auris even when therapy is delayed.

scholarly journals Survival, Persistence, and Isolation of the Emerging Multidrug-Resistant Pathogenic Yeast Candida auris on a Plastic Health Care Surface

2017 ◽  
Vol 55 (10) ◽  
pp. 2996-3005 ◽  
Author(s):  
Rory M. Welsh ◽  
Meghan L. Bentz ◽  
Alicia Shams ◽  
Hollis Houston ◽  
Amanda Lyons ◽  
...  
Keyword(s):  
Health Care ◽  
Multidrug Resistant ◽  
Health Care Facilities ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Content Type ◽  
Health Care Settings ◽  
Care Facilities ◽  
Enrichment Protocol ◽  
Plastic Surfaces

ABSTRACTThe emerging multidrug-resistant pathogenic yeastCandida aurisrepresents a serious threat to global health. Unlike most otherCandidaspecies, this organism appears to be commonly transmitted within health care facilities and causes health care-associated outbreaks. To better understand the epidemiology of this emerging pathogen, we investigated the ability ofC. auristo persist on plastic surfaces common in health care settings compared with that ofCandida parapsilosis, a species known to colonize the skin and plastics. Specifically, we compiled comparative and quantitative data essential to understanding the vehicles of spread and the ability of both species to survive and persist on plastic surfaces under controlled conditions (25°C and 57% relative humidity), such as those found in health care settings. When a test suspension of 104cells was applied and dried on plastic surfaces,C. aurisremained viable for at least 14 days andC. parapsilosisfor at least 28 days, as measured by CFU. However, survival measured by esterase activity was higher forC. auristhanC. parapsilosisthroughout the 28-day study. Given the notable length of timeCandidaspecies survive and persist outside their host, we developed methods to more effectively cultureC. aurisfrom patients and their environment. Using our enrichment protocol, public health laboratories and researchers can now readily isolateC. aurisfrom complex microbial communities (such as patient skin, nasopharynx, and stool) as well as environmental biofilms, in order to better understand and preventC. auriscolonization and transmission.

scholarly journals The environmental stress sensitivities of pathogenic Candida species, including Candida auris, and implications for their spread in the hospital setting

2020 ◽  
Vol 58 (6) ◽  
pp. 744-755 ◽  
Author(s):  
Helen Heaney ◽  
Juliette Laing ◽  
Linda Paterson ◽  
Alan W Walker ◽  
Neil A R Gow ◽  
...  
Keyword(s):  
Health Care ◽  
Candida Species ◽  
Hospital Setting ◽  
Low Ph ◽  
Antifungal Drugs ◽  
In Vitro Assays ◽  
Intrinsic Resistance ◽  
Candida Auris ◽  
Pathogenic Yeast

Abstract Candida auris is an emerging pathogenic yeast of significant clinical concern because of its frequent intrinsic resistance to fluconazole and often other antifungal drugs and the high mortality rates associated with systemic infections. Furthermore, C. auris has a propensity for persistence and transmission in health care environments. The reasons for this efficient transmission are not well understood, and therefore we tested whether enhanced resistance to environmental stresses might contribute to the ability of C. auris to spread in health care environments. We compared C. auris to other pathogenic Candida species with respect to their resistance to individual stresses and combinations of stresses. Stress resistance was examined using in vitro assays on laboratory media and also on hospital linen. In general, the 17 C. auris isolates examined displayed similar degrees of resistance to oxidative, nitrosative, cationic and cell wall stresses as clinical isolates of C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. lusitaniae and C. kefyr. All of the C. auris isolates examined were more sensitive to low pH (pH 2, but not pH 4) compared to C. albicans, but were more resistant to high pH (pH 13). C. auris was also sensitive to low pH, when tested on contaminated hospital linen. Most C. auris isolates were relatively thermotolerant, displaying significant growth at 47°C. Furthermore, C. auris was relatively resistant to certain combinations of combinatorial stress (e.g., pH 13 plus 47°C). Significantly, C. auris was sensitive to the stress combinations imposed by hospital laundering protocol (pH > 12 plus heat shock at >80°C), suggesting that current laundering procedures are sufficient to limit the transmission of this fungal pathogen via hospital linen.

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