scholarly journals Rapid and extensive karyotype diversification in haploid clinical Candida auris isolates

2019 ◽  
Author(s):  
Gustavo Bravo Ruiz ◽  
Zoe K. Ross ◽  
Silke Schelenz ◽  
Neil A.R. Gow ◽  
Alexander Lorenz
Keyword(s):  
Yeast Species ◽  
Time Frame ◽  
Drug Resistant ◽  
Simple Correlation ◽  
Candida Auris ◽  
Karyotype Variability ◽  
Recent Emergence ◽  
Short Time ◽  
Pathogenic Microbe ◽  
Karyotype Heterogeneity

Candida auris is a newly emerging pathogenic microbe, having been identified as a medically relevant fungus as recently as 2009. It is the most drug-resistant yeast species known to date and its emergence and population structure are unusual. Because of its recent emergence we are largely ignorant about fundamental aspects of its general biology, life cycle, and population dynamics. Here we report the karyotype variability of 26 C. auris strains representing the four main clades. We demonstrate that all strains are haploid and have a highly plastic karyotype containing five to seven chromosomes, which can undergo marked alterations within a short time-frame when the fungus is put under genotoxic, heat, or osmotic stress. No simple correlation was found between karyotype pattern, drug resistance, and clade affiliation indicating that karyotype heterogeneity is rapidly evolving. As with other Candida species, these marked karyotype differences between isolates are likely to have an important impact on pathogenic traits of C. auris.

scholarly journals Derivatives of the antimalarial drug mefloquine are broad spectrum antifungal molecules with activity against drug-resistant clinical isolates

2019 ◽  
Author(s):  
Marhiah C. Montoya ◽  
Sarah Beattie ◽  
Kathryn M. Alden ◽  
Damian J. Krysan
Keyword(s):  
Antifungal Activity ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
Clinical Isolates ◽  
In Vitro Toxicity ◽  
Drug Resistant ◽  
Candida Auris ◽  
Recent Emergence ◽  
Derivatives Of

ABSTRACTThe antifungal pharmacopeia is critically small, particularly in light of the recent emergence of multi-drug-resistant pathogens such as Candida auris. Herein, we report that derivatives of the anti-malarial drug mefloquine have broad spectrum antifungal activity against pathogenic yeasts and molds. In addition, the mefloquine derivatives have activity against clinical isolates that are resistant to one or more of the three classes of drugs currently used to treat invasive fungal infections, indicating that they have a novel mechanism of action. Importantly, the in vitro toxicity profiles using human cell lines indicate that the mefloquine derivatives are very similar to the parent mefloquine despite being up to 64-fold more active against fungal cells. In addition to direct antifungal activity, sub-inhibitory concentrations of the mefloquine derivatives inhibit the expression of virulence traits including filamentation in C. albicans and capsule formation/melanization in C. neoformans. Mode/mechanism of action experiments indicate that the mefloquine derivatives interfere with both mitochondrial and vacuolar function as part of a multi-target mechanism of action. The broad-spectrum scope of activity, blood-brain-barrier penetration, and large number of previously synthesized analogs available combine to support the further optimization and development of the antifungal activity of this general class of drug-like molecules.

scholarly journals Azole uptake in Candida auris is strongly correlated with drug resistance

2021 ◽  
Vol 3 (12) ◽  
Author(s):  
Brooke Esquivel ◽  
Theodore C. White
Keyword(s):  
Drug Resistance ◽  
Yeast Species ◽  
Fungal Species ◽  
Drug Uptake ◽  
Drug Resistant ◽  
Strongly Correlated ◽  
Potential Mechanism ◽  
Candida Auris ◽  
Fluconazole Resistance ◽  
Fluconazole Resistant

Analyses of fluconazole uptake in clinical isolates of C. auris, with wide ranging drug resistance profiles, has revealed interesting differences within the species as well as major distinctions from other yeast species. We previously proposed that prevention of drug uptake is a potential mechanism of drug resistance and our C. auris data provide further support for this. We developed an assay using radio-labeled fluconazole to measure intracellular azole accumulation in fungal cells. The assay is performed under glucose-replete conditions to inhibit ATP-dependent efflux. A comparative study measuring fluconazole uptake in 63 C. auris isolates as well as a panel of other species such as C. albicans, S. cerevisiae, C. glabrata, C. krusie, C. lusitanea, C. tropicalis, and C. dublinienses revealed striking C. auris phenotypes that we have not seen in other fungal species. There is a strong correlation between fluconazole resistance and reduced drug uptake in C. auris. Fluconazole-resistant C. auris isolates had reduced levels of intracellular fluconazole accumulation compared to susceptible isolates. Drug-resistant C. auris isolates had the lowest drug accumulation of any of the yeast species tested. Fluconazole-susceptible C. auris isolates had dramatically increased fluconazole accumulation compared to the resistant isolates as well as when compared to other yeast species. Of the 63 C. auris isolates, 28 of 32 (∼88%) resistant isolates had extremely low fluconazole uptake, whereas 15 of 18 (∼83%) susceptible isolates had high fluconazole uptake. This association between reduced drug uptake and resistance could be a C. auris-distinctive mechanism of drug resistance.

Candida auris and Nosocomial Infection

2020 ◽  
Vol 21 (4) ◽  
pp. 365-373 ◽  
Author(s):  
Sweety Dahiya ◽  
Anil K. Chhillar ◽  
Namita Sharma ◽  
Pooja Choudhary ◽  
Aruna Punia ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Pathogenic Fungus ◽  
Control Measures ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Drug Resistant ◽  
Candida Auris ◽  
Preventive Control ◽  
Identification Techniques ◽  
Sensitivity Profile

The existence of the multi-drug resistant (MDR) pathogenic fungus, Candida auris came to light in 2009. This particular organism is capable of causing nosocomial infections in immunecompromised persons. This pathogen is associated with consistent candidemia with high mortality rate and presents a serious global health threat. Whole genome sequence (WGS) investigation detected powerful phylogeographic Candida auris genotypes which are specialized to particular geological areas indicating dissemination of particular genotype among provinces. Furthermore, this organism frequently exhibits multidrug-resistance and displays an unusual sensitivity profile. Identification techniques that are commercialized to test Candida auris often show inconsistent results and this misidentification leads to treatment failure which complicates the management of candidiasis. Till date, Candida auris has been progressively recorded from several countries and therefore its preventive control measures are paramount to interrupt its transmission. In this review, we discussed prevalence, biology, drug-resistance phenomena, virulence factors and management of Candida auris infections.

scholarly journals Efficacy of compressed sodium chloride (CSC) against E. coli and Candida auris in minutes and methods improvement for testing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lan N. Truong ◽  
Brayden D. Whitlock
Keyword(s):  
Sodium Chloride ◽  
Improved Method ◽  
Candida Auris ◽  
Antimicrobial Surfaces ◽  
E Coli ◽  
Route Of Transmission ◽  
The World ◽  
Short Time ◽  
First Time ◽  
Time Point

AbstractControlling infections has become one of the biggest problems in the world, whether measured in lives lost or money spent. This is worsening as pathogens continue becoming resistant to therapeutics. Antimicrobial surfaces are one strategy being investigated in an attempt to decrease the spread of infections through the most common route of transmission: surfaces, including hands. Regulators have chosen two hours as the time point at which efficacy should be measured. The objectives of this study were to characterize the new antimicrobial surface compressed sodium chloride (CSC) so that its action may be understood at timepoints more relevant to real-time infection control, under two minutes; to develop a sensitive method to test efficacy at short time points; and to investigate antifungal properties for the first time. E. coli and Candida auris are added to surfaces, and the surfaces are monitored by contact plate, or by washing into collection vats. An improved method of testing antimicrobial efficacy is reported. Antimicrobial CSC achieves at least 99.9% reduction of E. coli in the first two minutes of contact, and at least 99% reduction of C. auris in one minute.

scholarly journals Polyethylene Migration from Food Packaging on Cheese Detected by Raman and Infrared (ATR/FT-IR) Spectroscopy

Materials ◽  
2021 ◽  
Vol 14 (14) ◽  
pp. 3872
Author(s):  
Klytaimnistra Katsara ◽  
George Kenanakis ◽  
Zacharias Viskadourakis ◽  
Vassilis M. Papadakis
Keyword(s):  
Vibrational Spectroscopy ◽  
Food Packaging ◽  
Time Frame ◽  
Low Density Polyethylene ◽  
Low Density ◽  
Ft Ir ◽  
Comparative Results ◽  
Short Time ◽  
And Storage ◽  
Ft Ir Spectroscopy

For multiple years, food packaging migration has been a major concern in food and health sciences. Plastics, such as polyethylene, are continuously utilized in food packaging for preservation and easy handling purposes during transportation and storage. In this work, three types of cheese, Edam, Kefalotyri and Parmesan, of different hardness were studied under two complementary vibrational spectroscopy methods, ATR-FTIR and Raman spectroscopy, to determine the migration of low-density polyethylene from plastic packaging to the surface of cheese samples. The experimental duration of this study was set to 28 days due to the degradation time of the selected cheese samples, which is clearly visible after 1 month in refrigerated conditions at 4 °C. Raman and ATR-FTIR measurements were performed at a 4–3–4–3 day pattern to obtain comparative results. Initially, consistency/repeatability measurement tests were performed on Day0 for each sample of all cheese specimens to understand if there is any overlap between the characteristic Raman and ATR-FTIR peaks of the cheese with the ones from the low-density polyethylene package. We provide evidence that on Day14, peaks of low-density polyethylene appeared due to polymeric migration in all three cheese types we tested. In all cheese samples, microbial outgrowth started to develop after Day21, as observed visually and under the bright-field microscope, causing peak reverse. Food packaging migration was validated using two different approaches of vibrational spectroscopy (Raman and FT-IR), revealing that cheese needs to be consumed within a short time frame in refrigerated conditions at 4 °C.

scholarly journals Breeding Strategies to Improve Miscanthus as a Sustainable Source of Biomass for Bioenergy and Biorenewable Products

Agronomy ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 673 ◽  
Author(s):  
John Clifton-Brown ◽  
Kai-Uwe Schwarz ◽  
Danny Awty-Carroll ◽  
Antonella Iurato ◽  
Heike Meyer ◽  
...  
Keyword(s):  
Significant Contribution ◽  
Perennial Grass ◽  
Time Frame ◽  
Eastern Asia ◽  
Germplasm Collections ◽  
Naturally Occurring ◽  
Wide Range ◽  
Yield Quality ◽  
Short Time ◽  
Commercial Expansion

Miscanthus, a C4 perennial grass native to Eastern Asia, is being bred to provide biomass for bioenergy and biorenewable products. Commercial expansion with the clonal hybrid M. × giganteus is limited by low multiplication rates, high establishment costs and drought sensitivity. These limitations can be overcome by breeding more resilient Miscanthus hybrids propagated by seed. Naturally occurring fast growing indigenous Miscanthus species are found in diverse environments across Eastern Asia. The natural diversity provides for plant breeders, the genetic resources to improve yield, quality, and resilience for a wide range of climates and adverse abiotic stresses. The challenge for Miscanthus breeding is to harness the diversity through selections of outstanding wild types, parents, and progenies over a short time frame to deploy hybrids that make a significant contribution to a world less dependent on fossil resources. Here are described the strategies taken by the Miscanthus breeding programme at Aberystwyth, UK and its partners. The programme built up one of the largest Miscanthus germplasm collections outside Asia. We describe the initial strategies to exploit the available genetic diversity to develop varieties. We illustrate the success of combining diverse Miscanthus germplasm and the selection criteria applied across different environments to identify promising hybrids and to develop these into commercial varieties. We discuss the potential for molecular selections to streamline the breeding process.

scholarly journals 1579. Multidrug-Resistant Candida auris Isolates From New York Hospitals and Healthcare Facilities Are Susceptible to Antifungal Combinations

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S576-S577
Author(s):  
Brittany O’Brien ◽  
Sudha Chaturvedi ◽  
Vishnu Chaturvedi
Keyword(s):  
New York ◽  
Diagnostic System ◽  
Multidrug Resistant ◽  
Drug Combinations ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Candida Auris ◽  
Current Case ◽  
Healthcare Facilities ◽  
Broth Microdilution Method

Abstract Background Candida auris outbreak continues unabated in New York with the current case counts exceeding 300 patients. We used a modification of standard CLSI broth microdilution method (BMD) if two-drug combinations are efficacious against C. auris isolates with high-resistance to fluconazole (FZ, MIC50 >256 mg/L), and variable resistance to other broad-spectrum antifungal drugs. Methods BMD plates were custom-designed and quality controlled by TREK Diagnostic System. The combination tests of 15 drug-resistant C. auris involved microtiter wells with the initial 144 two-drug combinations and their two-fold dilutions (1/2–1/32) to get 864 two-drug combinations finally. We utilized MIC100 endpoints for the drug combination readings as reported earlier for the intra- and inter-laboratory agreements obtained against Candida species and Aspergillus fumigatus (Antimicrob Agents Chemother. 2015. 59:1759–1766). We also tested minimum fungicidal concentrations (MFC). Results We tested all possible 864 two-drug antifungal combinations for nine antifungal drugs in use to yield 12,960 MIC100 readings, and MFC readings for 15 C. auris isolates. Flucytosine (FLC) at 2.0 mg/L potentiated most successful combinations with other drugs. Micafungin (MFG), Anidulafungin (AFG), Caspofungin (CAS) at individual concentrations of 0.25 mg/L combined well with FLC (2.0 mg/L) to yield MIC100 for 14, 13, and 12 of 15 C. auris isolates tested, respectively. MFG/FLC combination was also fungicidal for 4 of 15 isolates. AMB / FLC (0.25/1.0 mg/L) yielded MIC100 for 13 isolates and MFC for three test isolates. Posaconazole (POS), and Isavuconazole (ISA) and Voriconazole (VRC) also combined well with FLC (0.25/2.0 mg/L) to yield MIC100 for 12, 13, and 13 isolates, respectively. POS/FLC combination was fungicidal for three isolates. Conclusion We identified seven two drug-combinations of antifungals efficacious against drug-resistant C. auris strains. The modified BMD combination susceptibility testing could be used by the clinical laboratories to assist providers with the selection of optimal treatment for C. auris candidemia. Disclosures All authors: No reported disclosures.

Ranking the explanatory power of factors associated with worldwide new Covid-19 cases

2021 ◽  
Author(s):  
Aristides Moustakas
Keyword(s):  
Explanatory Power ◽  
Interdisciplinary Approach ◽  
Time Frame ◽  
Variance Partitioning ◽  
Total Variance ◽  
Disease Spread ◽  
Spatial Spread ◽  
Global Pandemic ◽  
Governmental Intervention ◽  
Short Time

Abstract Disease spread is a complex phenomenon requiring an interdisciplinary approach. Covid-19 exhibited a global spatial spread in a very short time frame resulting in a global pandemic. Data of new Covid-19 cases per million were analysed worldwide at the spatial scale of a country and time replicated from the end of December 2019 to late May 2020. Data driven analysis of epidemiological, economic, public health, and governmental intervention variables was performed in order to select the optimal variables in explaining new Covid-19 cases across all countries in time. Sequentially, hierarchical variance partitioning of the optimal variables was performed in order to quantify the independent contribution of each variable in the total variance of new Covid-19 cases per million. Results indicated that from the variables available new tests per thousand explained the vast majority of the total variance in new cases (51.6%) followed by the governmental stringency index (15.2%). Availability of hospital beds per 100k inhabitants explained 9% extreme poverty explained 8.8%, hand washing facilities 5.3%, the fraction of the population aged 65 or older explained 3.9%, and other disease prevalence (cardiovascular diseases plus diabetes) explained 2.9%. The percentage of smokers within the population explained 2.6% of the total variance, while population density explained 0.6%.

Crossword Puzzles: Active Learning in Undergraduate Pathology and Medical Education

2009 ◽  
Vol 133 (9) ◽  
pp. 1457-1462
Author(s):  
Anurag Saxena ◽  
Raenelle Nesbitt ◽  
Punam Pahwa ◽  
Sheryl Mills
Keyword(s):  
Student Perceptions ◽  
Small Groups ◽  
Time Frame ◽  
Teaching Tool ◽  
Internet Resource ◽  
Cooperative Groups ◽  
Key Concepts ◽  
Second Year ◽  
Peer Teachers ◽  
Short Time

Abstract Context.—Second-year medical students are introduced to many new terms and concepts in a short time frame in the hematology system and the neoplasia section of the undergraduate pathology course. It is a challenge to provide adequate practice and necessary repetition to reinforce key concepts. Objective.—To determine student perceptions of the usefulness of crosswords as a quick and effective way to reinforce essential concepts and vocabulary. Design.—Crosswords with ensured content validity built on a free Internet resource were completed by the students in collaborative and cooperative groups of 6 to 7 with a reward for the first group to successfully complete the puzzle. Student perceptions of the value of crosswords for their learning were examined in 2003 (39 students) with a survey of yes or no responses and in 2004 (41 students) with a survey using questions with a 5-point Likert scale. Results.—Many students (37 of 39 in 2003 and 24 of 41 in 2004) indicated that crosswords were useful and contributed to their learning. Specifically, crosswords were found to be useful for identifying key concepts and vocabulary and for their collaborative and competitive aspects. Written and informal comments indicated student enthusiasm for and a desire to participate in more of these exercises. Students have transferred this review strategy to other classes and the peer teachers have expressed an interest in it as an adjunct teaching tool. Conclusions.—The judicious use of crosswords was useful for near transfer content and provided an opportunity to discuss and recall essential concepts, think critically, and collaborate in small groups.

scholarly journals MONITORING THE RESISTANCE OF CLINICAL STRAINS OF CANDIDA YEAST TO FLUCONAZOLE (A BRIEF LITERATURE REVIEW)

2017 ◽  
pp. 70-74 ◽  
Author(s):  
T. M. Zheltikova
Keyword(s):  
Literature Review ◽  
Yeast Species ◽  
Geographical Location ◽  
Vulvovaginal Candidiasis ◽  
Drug Resistant ◽  
The Past ◽  
Fluconazole Resistant ◽  
Resistant Strains ◽  
The Moment ◽  
Drug Resistant Strains

The article analyzes the global and national research on the resistance of Candida yeasts to fluconazole. The studies demonstrate that the formation of resistance is determined by many factors: type of yeast, choice of the antimycotic medication, geographical location, etc. In addition, one can not disregard the socio-economic and even political causes. The frequency of detection of drug-resistant strains of different species of Candida yeast to fluconazole varies across different regions, between countries of the same region, and may vary from year to year within a country. In other words, the formation of yeast resistance/ susceptibility to fluconazole, and to other antifungals alike, is dynamic and may be reversible.Therefore, both global and national studies conducted over the past decades and devoted to the formation of resistance of Candida yeast to azoles, in particular, fluconazole, have shown that it is still the medication of choice for the treatment of candidiasis, including acute vulvovaginal candidiasis, as well as for relief and prevention of exacerbations of recurrent vulvovaginal candidiasis. C. krusei was and remains one of the most fluconazole-resistant yeast species. Other species, such as C. inconspicua and C. norvegensis, the number and incidence of which is too low for the moment to make any statistically valid conclusions, may in the future be added to the list. 

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