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Issue 34, 2019
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Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile

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Abstract

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.

Graphical abstract: Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile

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Supplementary files

Article information


Submitted
14 Feb 2019
Accepted
04 Apr 2019
First published
04 Apr 2019

Chem. Commun., 2019,55, 5009-5012
Article type
Communication

Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile

N. D. Danielson, J. Collins, A. I. Stothard, Q. Q. Dong, K. Kalera, P. J. Woodruff, B. J. DeBosch, R. A. Britton and B. M. Swarts, Chem. Commun., 2019, 55, 5009
DOI: 10.1039/C9CC01300H

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