Novel, synergistic antifungal combinations that target translation fidelity
There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different...
| Main Authors: | , , , |
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| Format: | Article |
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Nature Publishing Group
2015
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| Online Access: | https://eprints.nottingham.ac.uk/40884/ |
| _version_ | 1848796154846773248 |
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| author | Moreno-Martinez, Elena Vallieres, Cindy Holland, Sara L. Avery, Simon V. |
| author_facet | Moreno-Martinez, Elena Vallieres, Cindy Holland, Sara L. Avery, Simon V. |
| author_sort | Moreno-Martinez, Elena |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8 fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. |
| first_indexed | 2025-11-14T19:43:29Z |
| format | Article |
| id | nottingham-40884 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:43:29Z |
| publishDate | 2015 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-408842020-05-04T17:22:44Z https://eprints.nottingham.ac.uk/40884/ Novel, synergistic antifungal combinations that target translation fidelity Moreno-Martinez, Elena Vallieres, Cindy Holland, Sara L. Avery, Simon V. There is an unmet need for new antifungal or fungicide treatments, as resistance to existing treatments grows. Combination treatments help to combat resistance. Here we develop a novel, effective target for combination antifungal therapy. Different aminoglycoside antibiotics combined with different sulphate-transport inhibitors produced strong, synergistic growth-inhibition of several fungi. Combinations decreased the respective MICs by ≥8 fold. Synergy was suppressed in yeast mutants resistant to effects of sulphate-mimetics (like chromate or molybdate) on sulphate transport. By different mechanisms, aminoglycosides and inhibition of sulphate transport cause errors in mRNA translation. The mistranslation rate was stimulated up to 10-fold when the agents were used in combination, consistent with this being the mode of synergistic action. A range of undesirable fungi were susceptible to synergistic inhibition by the combinations, including the human pathogens Candida albicans, C. glabrata and Cryptococcus neoformans, the food spoilage organism Zygosaccharomyces bailii and the phytopathogens Rhizoctonia solani and Zymoseptoria tritici. There was some specificity as certain fungi were unaffected. There was no synergy against bacterial or mammalian cells. The results indicate that translation fidelity is a promising new target for combinatorial treatment of undesirable fungi, the combinations requiring substantially decreased doses of active components compared to each agent alone. Nature Publishing Group 2015-11-17 Article PeerReviewed Moreno-Martinez, Elena, Vallieres, Cindy, Holland, Sara L. and Avery, Simon V. (2015) Novel, synergistic antifungal combinations that target translation fidelity. Scientific Reports, 5 (16700). pp. 1-11. ISSN 2045-2322 http://www.nature.com/articles/srep16700 doi:10.1038/srep16700 doi:10.1038/srep16700 |
| spellingShingle | Moreno-Martinez, Elena Vallieres, Cindy Holland, Sara L. Avery, Simon V. Novel, synergistic antifungal combinations that target translation fidelity |
| title | Novel, synergistic antifungal combinations that target
translation fidelity |
| title_full | Novel, synergistic antifungal combinations that target
translation fidelity |
| title_fullStr | Novel, synergistic antifungal combinations that target
translation fidelity |
| title_full_unstemmed | Novel, synergistic antifungal combinations that target
translation fidelity |
| title_short | Novel, synergistic antifungal combinations that target
translation fidelity |
| title_sort | novel, synergistic antifungal combinations that target
translation fidelity |
| url | https://eprints.nottingham.ac.uk/40884/ https://eprints.nottingham.ac.uk/40884/ https://eprints.nottingham.ac.uk/40884/ |