Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile
| Autor: | Alicyn I Stothard, Brian J. DeBosch, Qing Qing Dong, Peter J. Woodruff, Benjamin M. Swarts, Karishma Kalera, James J. Collins, Robert A. Britton, Noah D. Danielson |
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| Rok vydání: | 2019 |
| Předmět: |
Swine
Virulence 010402 general chemistry 01 natural sciences Article Catalysis chemistry.chemical_compound Carbon source Carbohydrate Conformation Materials Chemistry Animals Trehalase chemistry.chemical_classification Dose-Response Relationship Drug Clostridioides difficile 010405 organic chemistry Chemistry Metals and Alloys Trehalose General Chemistry 0104 chemical sciences Surfaces Coatings and Films Electronic Optical and Magnetic Materials Enzyme Biochemistry Ceramics and Composites Degradation (geology) Clostridioides Validamycin A |
| Zdroj: | Chemical Communications. 55:5009-5012 |
| ISSN: | 1364-548X 1359-7345 |
| Popis: | Trehalose is used as an additive in thousands of foods, cosmetics, and pharmaceutical products, and it is being investigated as a therapeutic for multiple human diseases. However, its ability to be used as a carbon source by microbes is a concern, as highlighted by the recent finding that trehalose can be metabolized by and potentially enhance the virulence of epidemic Clostridioides difficile. Here, we show that trehalose analogues designed to resist enzymatic degradation are incapable of being used as carbon sources by C. difficile. Furthermore, we demonstrate that trehalose analogues, but not the known trehalase inhibitor validamycin A, inhibit native trehalose utilization by hypervirulent C. difficile. Thus, degradation-resistant trehalose analogues are valuable as trehalase inhibitors and as surrogates for or co-additives with trehalose in applications where enzymatic breakdown is a concern. |
| Databáze: | OpenAIRE |
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