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Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile.
Chem Commun (Camb) 2019; 55(34):5009-5012CC

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.

Authors+Show Affiliations

Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA. ben.swarts@cmich.edu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30968891

Citation

Danielson, Noah D., et al. "Degradation-resistant Trehalose Analogues Block Utilization of Trehalose By Hypervirulent Clostridioides Difficile." Chemical Communications (Cambridge, England), vol. 55, no. 34, 2019, pp. 5009-5012.
Danielson ND, Collins J, Stothard AI, et al. Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile. Chem Commun (Camb). 2019;55(34):5009-5012.
Danielson, N. D., Collins, J., Stothard, A. I., Dong, Q. Q., Kalera, K., Woodruff, P. J., ... Swarts, B. M. (2019). Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile. Chemical Communications (Cambridge, England), 55(34), pp. 5009-5012. doi:10.1039/c9cc01300h.
Danielson ND, et al. Degradation-resistant Trehalose Analogues Block Utilization of Trehalose By Hypervirulent Clostridioides Difficile. Chem Commun (Camb). 2019 Apr 23;55(34):5009-5012. PubMed PMID: 30968891.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile. AU - Danielson,Noah D, AU - Collins,James, AU - Stothard,Alicyn I, AU - Dong,Qing Qing, AU - Kalera,Karishma, AU - Woodruff,Peter J, AU - DeBosch,Brian J, AU - Britton,Robert A, AU - Swarts,Benjamin M, PY - 2020/04/23/pmc-release PY - 2019/4/11/pubmed PY - 2019/5/8/medline PY - 2019/4/11/entrez SP - 5009 EP - 5012 JF - Chemical communications (Cambridge, England) JO - Chem. Commun. (Camb.) VL - 55 IS - 34 N2 - 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. SN - 1364-548X UR - https://www.unboundmedicine.com/medline/citation/30968891/Degradation-resistant_trehalose_analogues_block_utilization_of_trehalose_by_hypervirulent_Clostridioides_difficile L2 - https://doi.org/10.1039/c9cc01300h DB - PRIME DP - Unbound Medicine ER -