Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae
Since the earliest days of using natural remedies, combining therapies for disease treatment has been standard practice. Combination treatments exhibit synergistic effects, broadly defined as a greater-than-additive effect of two or more therapeutic agents. Clinicians often use their experience and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-07-01
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| Series: | Frontiers in Fungal Biology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/ffunb.2021.683414/full |
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| author | Hamid Gaikani Hamid Gaikani Andrew M. Smith Anna Y. Lee Guri Giaever Corey Nislow Corey Nislow |
| author_facet | Hamid Gaikani Hamid Gaikani Andrew M. Smith Anna Y. Lee Guri Giaever Corey Nislow Corey Nislow |
| author_sort | Hamid Gaikani |
| collection | DOAJ |
| description | Since the earliest days of using natural remedies, combining therapies for disease treatment has been standard practice. Combination treatments exhibit synergistic effects, broadly defined as a greater-than-additive effect of two or more therapeutic agents. Clinicians often use their experience and expertise to tailor such combinations to maximize the therapeutic effect. Although understanding and predicting biophysical underpinnings of synergy have benefitted from high-throughput screening and computational studies, one challenge is how to best design and analyze the results of synergy studies, especially because the number of possible combinations to test quickly becomes unmanageable. Nevertheless, the benefits of such studies are clear—by combining multiple drugs in the treatment of infectious disease and cancer, for instance, one can lessen host toxicity and simultaneously reduce the likelihood of resistance to treatment. This study introduces a new approach to characterize drug synergy, in which we extend the widely validated chemogenomic HIP–HOP assay to drug combinations; this assay involves parallel screening of comprehensive collections of barcoded deletion mutants. We identify a class of “combination-specific sensitive strains” that introduces mechanisms for the synergies we observe and further suggest focused follow-up studies. |
| first_indexed | 2024-12-22T15:21:18Z |
| format | Article |
| id | doaj.art-85acc49a7dbb41fda471bb31da374a4c |
| institution | Directory Open Access Journal |
| issn | 2673-6128 |
| language | English |
| last_indexed | 2024-12-22T15:21:18Z |
| publishDate | 2021-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Fungal Biology |
| spelling | doaj.art-85acc49a7dbb41fda471bb31da374a4c2022-12-21T18:21:36ZengFrontiers Media S.A.Frontiers in Fungal Biology2673-61282021-07-01210.3389/ffunb.2021.683414683414Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiaeHamid Gaikani0Hamid Gaikani1Andrew M. Smith2Anna Y. Lee3Guri Giaever4Corey Nislow5Corey Nislow6Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaDepartment of Chemistry, University of British Columbia, Vancouver, BC, CanadaDonnelly Centre for Cellular and Biomedical Research, University of Toronto, Toronto, ON, CanadaDonnelly Centre for Cellular and Biomedical Research, University of Toronto, Toronto, ON, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaFaculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, CanadaDepartment of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, CanadaSince the earliest days of using natural remedies, combining therapies for disease treatment has been standard practice. Combination treatments exhibit synergistic effects, broadly defined as a greater-than-additive effect of two or more therapeutic agents. Clinicians often use their experience and expertise to tailor such combinations to maximize the therapeutic effect. Although understanding and predicting biophysical underpinnings of synergy have benefitted from high-throughput screening and computational studies, one challenge is how to best design and analyze the results of synergy studies, especially because the number of possible combinations to test quickly becomes unmanageable. Nevertheless, the benefits of such studies are clear—by combining multiple drugs in the treatment of infectious disease and cancer, for instance, one can lessen host toxicity and simultaneously reduce the likelihood of resistance to treatment. This study introduces a new approach to characterize drug synergy, in which we extend the widely validated chemogenomic HIP–HOP assay to drug combinations; this assay involves parallel screening of comprehensive collections of barcoded deletion mutants. We identify a class of “combination-specific sensitive strains” that introduces mechanisms for the synergies we observe and further suggest focused follow-up studies.https://www.frontiersin.org/articles/10.3389/ffunb.2021.683414/fulldrug synergydrug combinationsdrug–gene interactionantifungalchemogenomics |
| spellingShingle | Hamid Gaikani Hamid Gaikani Andrew M. Smith Anna Y. Lee Guri Giaever Corey Nislow Corey Nislow Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae Frontiers in Fungal Biology drug synergy drug combinations drug–gene interaction antifungal chemogenomics |
| title | Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae |
| title_full | Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae |
| title_fullStr | Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae |
| title_full_unstemmed | Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae |
| title_short | Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae |
| title_sort | systematic prediction of antifungal drug synergy by chemogenomic screening in saccharomyces cerevisiae |
| topic | drug synergy drug combinations drug–gene interaction antifungal chemogenomics |
| url | https://www.frontiersin.org/articles/10.3389/ffunb.2021.683414/full |
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