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

Noah D. Danielson, James Collins, Alicyn I. Stothard, Qing Qing Dong, Karishma Kalera, Peter J. Woodruff, Brian J. Debosch, Robert A. Britton, Benjamin M. Swarts

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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.

Original languageEnglish
Pages (from-to)5009-5012
Number of pages4
JournalChemical Communications
Issue number34
StatePublished - 2019


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