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39 results for “azole resistance”
Azole resistance mechanisms and population structure of Aspergillus fumigatus on retail plant products
<p><em>Aspergillus fumigatus </em>is a ubiquitous saprotroph and human-pathogenic fungus that is life-threatening to the immunocompromised. Triazole-resistant <em>A. fumigatus</em><em> </em>was found in patients without prior treatment with azoles, leading researchers to conclude that resistance had developed in agricultural environments where azoles are used against plant pathogens. Previous studies have documented azole-resistant <em>A. fumigatus </em>across agricultural environments, but few have looked at retail plant products. Our objectives were to determine if azole-resistant <em>A. fumigatus </em>is prevalent<em> </em>in retail plant products produced in the United States (U.S.), as well as to identify the resistance mechanism(s) and population genetic structure of these isolates. Five hundred twenty-five isolates were collected from retail plant products and screened for azole resistance. Twenty-four isolates collected from compost, soil, flower bulbs, and raw peanuts were pan-azole resistant. Resistant isolates had the TR<sub>34</sub>/L98H, TR<sub>46</sub>/Y121F/T289A, G448S, and H147Y <em>cyp51A </em>alleles, all known to underly pan-azole resistance, as well as WT alleles, suggesting that non-cyp51A-mechanisms contribute to pan-azole resistance in some isolates. Minimum spanning networks showed two lineages containing isolates with TR alleles or the F46Y/M172V/E427K allele, and discriminant analysis of principle components (DAPC) identified three primary clusters. This is consistent with previous studies detecting three clades of <em>A. fumigatus</em> and identifying pan-azole-resistant isolates with TR alleles in a single clade. We found pan-azole resistance in U.S. retail plant products, particularly compost and flower bulbs, which indicates the risk of exposure to these products for susceptible populations and that highly resistant isolates are likely distributed worldwide on these products.</p>
Azole resistance mechanisms and population structure of Aspergillus fumigatus on retail plant products
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Data from: Asexual sporulation facilitates adaptation: the emergence of azole resistance in Aspergillus fumigatus
Understanding the occurrence and spread of azole resistance in Aspergillus fumigatus is crucial for public health. It has been hypothesized that asexual sporulation, which is abundant in nature, is essential for phenotypic expression of azole-resistance mutations in A. fumigatus facilitating subsequent spread through natural selection. Furthermore, the disease aspergilloma is associated with asexual sporulation within the lungs of patients and the emergence of azole resistance. This study assessed the evolutionary advantage of asexual sporulation by growing the fungus under pressure of one of five different azole fungicides over seven weeks and by comparing the rate of adaptation between scenarios of culturing with and without asexual sporulation. Results unequivocally show that asexual sporulation facilitates adaptation. This can be explained by the combination of more effective selection because of the transition from a multicellular to a unicellular stage, and by increased mutation supply due to the production of spores, which involves numerous mitotic divisions. Insights from this study are essential to unravel the resistance mechanisms of sporulating pathogens to chemical compounds and disease agents in general, and for designing strategies that prevent or overcome the emerging threat of azole resistance in particular.
Azole Susceptibility and Resistance Mechanisms Surveys in Pathogenic Fungi by the CARST-fungi (2023-2024)
ClinicalTrials.gov study NCT06969703. IPD Sharing: YES. Countries: 1. Publications: 2.
PCR Based Detection of Azole Resistance in A. Fumigatus to Improve Patient Outcome.
ClinicalTrials.gov study NCT03121235. IPD Sharing: UNDECIDED. Countries: 1. Publications: 9.
Data from: Asexual sporulation facilitates adaptation: the emergence of azole resistance in Aspergillus fumigatus
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Data from: Relevance of heterokaryosis for adaptation and azole-resistance development in Aspergillus fumigatus
Aspergillus fumigatus causes a range of diseases in humans, some of which are characterized by fungal persistence. A. fumigatus, being a generalist saprotroph, may initially establish lung colonisation due to its physiological versatility and subsequently adapt through genetic changes to the human lung environment and antifungal treatments. Human lung-adapted genotypes can arise by spontaneous mutation and/or recombination and subsequent selection of the fittest genotypes. Sexual and asexual spores are considered crucial contributors to the genetic diversity and adaptive potential of aspergilli by recombination and mutation supply respectively. However, in certain Aspergillus diseases, such as cystic fibrosis and chronic pulmonary aspergillosis, A. fumigatus may not sporulate but persist as a network of fungal mycelium. During azole therapy, such mycelia may develop patient-acquired resistance and become heterokaryotic by mutations in one of the nuclei. We investigated the relevance of heterokaryosis for azole-resistance development in A. fumigatus. We found evidence for heterokaryosis of A. fumigatus in patients with chronic Aspergillus diseases. Mycelium from patient-tissue biopsies segregated different homokaryons, from which heterokaryons could be reconstructed. Whereas all variant homokaryons recovered from the same patient were capable of forming a heterokaryon, those from different patients were heterokaryon-incompatible. We furthermore compared heterokaryons and heterozygous diploids constructed from environmental isolates with different levels of azole resistance. When exposed to azole, the heterokaryons revealed remarkable shifts in their nuclear ratio, and the resistance level of heterokaryons exceeded that of the corresponding heterozygous diploids.
Efflux Pump Mediated Azole Resistance in Candida Albicans
ClinicalTrials.gov study NCT03659162. IPD Sharing: UNDECIDED. Countries: 0. Publications: 10.
Data from: Relevance of heterokaryosis for adaptation and azole-resistance development in Aspergillus fumigatus
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Potent synergistic interactions between lopinavir and azole antifungal drugs against emerging multidrug-resistant Candida auris
GEO Series GSE148341. Candidozyma auris. 4 samples. Type: Expression profiling by high throughput sequencing.
Exploring comparative and transcriptomic analyses to unveil mechanisms of resistance to azoles dependent and independent of CgPdr1 in Candida glabrata clinical isolates
GEO Series GSE166841. Nakaseomyces glabratus. 14 samples. Type: Expression profiling by array.
AtrR is an essential determinant of azole resistance in Aspergillus fumigatus
GEO Series GSE123446. Aspergillus fumigatus Af293. 14 samples. Type: Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing.
Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata
GEO Series GSE23829. Nakaseomyces glabratus; Nakaseomyces glabratus CBS 138. 33 samples. Type: Expression profiling by array.
Azole Resistance Mechanism in Candida glabrata
GEO Series GSE21355. Nakaseomyces glabratus; Nakaseomyces glabratus CBS 138. 8 samples. Type: Expression profiling by array.
Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata (part 1)
GEO Series GSE23827. Nakaseomyces glabratus; Nakaseomyces glabratus CBS 138. 27 samples. Type: Expression profiling by array.
Use of Bulk Segregant Analysis for Determining the Genetic Basis of Azole Resistance in the Opportunistic Pathogen Aspergillus fumigatus
GEO Series GSE193956. Aspergillus fumigatus. 18 samples. Type: Genome variation profiling by high throughput sequencing.
Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata (part 2)
GEO Series GSE23828. Nakaseomyces glabratus CBS 138; Nakaseomyces glabratus. 6 samples. Type: Expression profiling by array.
Mutations in TAC1B drive increased CDR1 and MDR1 expression and azole resistance in Candida auris
GEO Series GSE288372. Candidozyma auris. 12 samples. Type: Expression profiling by high throughput sequencing.
Clinical Implications of Azole-Resistant Aspergillosis in Hematological Malignancy
ClinicalTrials.gov study NCT03221075. IPD Sharing: NO. Countries: 2. Publications: 0.
AspergillusOne-Health: Deciphering Azole Resistance in Aspergillus Fungi Using a One Health Approach
ClinicalTrials.gov study NCT06532227. IPD Sharing: Not stated. Countries: 0. Publications: 0.
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Allen Brain Atlas
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International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.