@article{e69a50780c2f4b0aa678930a97fefc6c,
title = "Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent: Clostridioides difficile",
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.",
author = "Danielson, {Noah D.} and James Collins and Stothard, {Alicyn I.} and Dong, {Qing Qing} and Karishma Kalera and Woodruff, {Peter J.} and Debosch, {Brian J.} and Britton, {Robert A.} and Swarts, {Benjamin M.}",
note = "Funding Information: This work was funded by a grant to B. M. S. and P. J. W. from the National Institutes of Health (R15AI117670), as well as a Henry Dreyfus Teacher-Scholar Award to B. M. S from The Camille & Henry Dreyfus Foundation (TH-17-034). This work was also supported by grants to R. A. B. from the National Institute of Allergy and Infectious Disease at the NIH (R01AI123278 and U01AI124290). This work was also supported by grants to B. J. D. from the NIH (R56 DK115764), Children{\textquoteright}s Discovery Institute (MI-FR-2014-426 and MI-II2017-593), AGA-Gilead Sciences Research Scholar Award in Liver Disease, The AGA-Allergan Pilot Research Award in Non-Alcoholic Fatty Liver Disease, and the Robert Wood Johnson Foundation. Dr Daniel Holmes of the Michigan State University NMR Facility is thanked for assistance with EXSIDE experiments. Dr Mallary Wacker is thanked for assistance with the mammalian cell toxicity experiments. Publisher Copyright: {\textcopyright} The Royal Society of Chemistry 2019.",
year = "2019",
doi = "10.1039/c9cc01300h",
language = "English",
volume = "55",
pages = "5009--5012",
journal = "Chemical Communications",
issn = "1359-7345",
number = "34",
}