Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i>
Antimicrobial resistance is a global health crisis to which pathogenic fungi make a substantial contribution. The human fungal pathogen <i>C. auris</i> is of particular concern due to its rapid spread across the world and its evolution of multidrug resistance. Fluconazole failure in <...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/3/898 |
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| author | Samira Rasouli Koohi Shamanth A. Shankarnarayan Clare Maristela Galon Daniel A. Charlebois |
| author_facet | Samira Rasouli Koohi Shamanth A. Shankarnarayan Clare Maristela Galon Daniel A. Charlebois |
| author_sort | Samira Rasouli Koohi |
| collection | DOAJ |
| description | Antimicrobial resistance is a global health crisis to which pathogenic fungi make a substantial contribution. The human fungal pathogen <i>C. auris</i> is of particular concern due to its rapid spread across the world and its evolution of multidrug resistance. Fluconazole failure in <i>C. auris</i> has been recently attributed to antifungal “tolerance”. Tolerance is a phenomenon whereby a slow-growing subpopulation of tolerant cells, which are genetically identical to susceptible cells, emerges during drug treatment. We use microbroth dilution and disk diffusion assays, together with image analysis, to investigate antifungal tolerance in <i>C. auris</i> to all three classes of antifungal drugs used to treat invasive candidiasis. We find that (1) <i>C. auris</i> is tolerant to several common fungistatic and fungicidal drugs, which in some cases can be detected after 24 h, as well as after 48 h, of antifungal drug exposure; (2) the tolerant phenotype reverts to the susceptible phenotype in <i>C. auris</i>; and (3) combining azole, polyene, and echinocandin antifungal drugs with the adjuvant chloroquine in some cases reduces or eliminates tolerance and resistance in patient-derived <i>C. auris</i> isolates. These results suggest that tolerance contributes to treatment failure in <i>C. auris</i> infections for a broad range of antifungal drugs, and that antifungal adjuvants may improve treatment outcomes for patients infected with antifungal-tolerant or antifungal-resistant fungal pathogens. |
| first_indexed | 2024-03-11T06:53:29Z |
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| id | doaj.art-52ae006e289643a998192c1c7c020073 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T06:53:29Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-52ae006e289643a998192c1c7c0200732023-11-17T09:47:13ZengMDPI AGBiomedicines2227-90592023-03-0111389810.3390/biomedicines11030898Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i>Samira Rasouli Koohi0Shamanth A. Shankarnarayan1Clare Maristela Galon2Daniel A. Charlebois3Department of Physics, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Physics, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Physics, University of Alberta, Edmonton, AB T6G 2R3, CanadaDepartment of Physics, University of Alberta, Edmonton, AB T6G 2R3, CanadaAntimicrobial resistance is a global health crisis to which pathogenic fungi make a substantial contribution. The human fungal pathogen <i>C. auris</i> is of particular concern due to its rapid spread across the world and its evolution of multidrug resistance. Fluconazole failure in <i>C. auris</i> has been recently attributed to antifungal “tolerance”. Tolerance is a phenomenon whereby a slow-growing subpopulation of tolerant cells, which are genetically identical to susceptible cells, emerges during drug treatment. We use microbroth dilution and disk diffusion assays, together with image analysis, to investigate antifungal tolerance in <i>C. auris</i> to all three classes of antifungal drugs used to treat invasive candidiasis. We find that (1) <i>C. auris</i> is tolerant to several common fungistatic and fungicidal drugs, which in some cases can be detected after 24 h, as well as after 48 h, of antifungal drug exposure; (2) the tolerant phenotype reverts to the susceptible phenotype in <i>C. auris</i>; and (3) combining azole, polyene, and echinocandin antifungal drugs with the adjuvant chloroquine in some cases reduces or eliminates tolerance and resistance in patient-derived <i>C. auris</i> isolates. These results suggest that tolerance contributes to treatment failure in <i>C. auris</i> infections for a broad range of antifungal drugs, and that antifungal adjuvants may improve treatment outcomes for patients infected with antifungal-tolerant or antifungal-resistant fungal pathogens.https://www.mdpi.com/2227-9059/11/3/898adjuvantantifungal tolerance/resistancebroth microdilution assay<i>Candida auris</i>disk diffusion assaydiskImageR |
| spellingShingle | Samira Rasouli Koohi Shamanth A. Shankarnarayan Clare Maristela Galon Daniel A. Charlebois Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i> Biomedicines adjuvant antifungal tolerance/resistance broth microdilution assay <i>Candida auris</i> disk diffusion assay diskImageR |
| title | Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i> |
| title_full | Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i> |
| title_fullStr | Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i> |
| title_full_unstemmed | Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i> |
| title_short | Identification and Elimination of Antifungal Tolerance in <i>Candida auris</i> |
| title_sort | identification and elimination of antifungal tolerance in i candida auris i |
| topic | adjuvant antifungal tolerance/resistance broth microdilution assay <i>Candida auris</i> disk diffusion assay diskImageR |
| url | https://www.mdpi.com/2227-9059/11/3/898 |
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