Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile
Year: 2019
Type: article
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.
Source: Chemical Communications
DOI: 10.1039/c9cc01300h
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: Robert Wood Johnson Foundation, Camille and Henry Dreyfus Foundation, Children's Discovery Institute, American Gastroenterological Association, National Institutes of Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1129610503, Chemoenzymatic synthesis of trehalose analogues as tools for investigating mycobacteria, G4504562259, Decoding Antibiotic-induced Susceptibility to Clostridium difficile Infection, Diet driven evolution of epidemic ribotypes of Clostridium difficile, G8048154552, Leveraging glucose transport and the adaptive fasting response to modulate hepatic metabolism
OpenAlex ID: W2935515067