Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficileElectronic supplementary information (ESI) available: Experimental methods and supporting data. See DOI: 10.1039/c9cc01300h

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...

Full description

Saved in:
Bibliographic Details
Main Authors: Danielson, Noah D, Collins, James, Stothard, Alicyn I, Dong, Qing Qing, Kalera, Karishma, Woodruff, Peter J, DeBosch, Brian J, Britton, Robert A, Swarts, Benjamin M
Format: Article
Language:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Trehalose analogues designed to resist enzymatic hydrolysis are the first inhibitors of hypervirulence-associated trehalose metabolism in the pathogen Clostridioides difficile .
ISSN:1359-7345
1364-548X
DOI:10.1039/c9cc01300h