Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile
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...
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| Veröffentlicht in: | Chemical communications (Cambridge, England) England), 2019-04, Vol.55 (34), p.5009-5012 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1039/c9cc01300h |
| format | Article |
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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. 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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.</description><subject>Additives</subject><subject>Animals</subject><subject>Carbohydrate Conformation</subject><subject>Carbon</subject><subject>chemical compounds</subject><subject>chemical reactions</subject><subject>Clostridioides difficile - drug effects</subject><subject>Clostridioides difficile - metabolism</subject><subject>Clostridium difficile</subject><subject>Cosmetics</subject><subject>Degradation</subject><subject>Dose-Response Relationship, Drug</subject><subject>drugs</subject><subject>enzyme inhibitors</subject><subject>Epidemics</subject><subject>foods</subject><subject>human diseases</subject><subject>Human performance</subject><subject>microorganisms</subject><subject>Swine</subject><subject>therapeutics</subject><subject>trehalase</subject><subject>Trehalase - antagonists & inhibitors</subject><subject>Trehalase - metabolism</subject><subject>Trehalose</subject><subject>Trehalose - chemistry</subject><subject>Trehalose - metabolism</subject><subject>Trehalose - pharmacology</subject><subject>Virulence</subject><issn>1359-7345</issn><issn>1364-548X</issn><issn>1364-548X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v3CAQhlHVqvloL_kBkaVeqkhuwIAxl0qRmy8pUi6p1BvCMOySsmYLdqTNry-bpFHSU7jMiHl4mZkXoQOCvxFM5bGRxmBCMV6-Q7uEtqzmrPv1fptzWQvK-A7ay_kWl0N49xHtUCzbrpNkF6UfsEja6snHsU6QfZ70OFVTgqUOMUOlxxIXM-RqCNH8rubJB3__wFfRvQCHTbXcrCHd-TQHKBp9uZ6Stz56W55b75w3PsAn9MHpkOHzU9xHP89Ob_qL-ur6_LI_uaoNo3KqB-zAAO84CAplTiExNI11JSG04x2T2GgGuB2EYG2pc-Ocaa21lDXAOrqPvj_qrudhBdaUnpIOap38SqeNitqr15XRL9Ui3qmWSUkFKQJfnwRS_FM2MKmVzwZC0CPEOaumKZ8yJil-A4oFaQkRW_TLf-htnFPZ8pYijcCSNbxQR4-USTHnBO65b4LV1nXVy75_cP2iwIcvJ31G_9lM_wL0pKqc</recordid><startdate>20190423</startdate><enddate>20190423</enddate><creator>Danielson, Noah D</creator><creator>Collins, James</creator><creator>Stothard, Alicyn I</creator><creator>Dong, Qing Qing</creator><creator>Kalera, Karishma</creator><creator>Woodruff, Peter J</creator><creator>DeBosch, Brian J</creator><creator>Britton, Robert A</creator><creator>Swarts, Benjamin M</creator><general>Royal Society of Chemistry</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2479-5189</orcidid><orcidid>https://orcid.org/0000-0001-8402-359X</orcidid><orcidid>https://orcid.org/0000-0002-9924-7921</orcidid><orcidid>https://orcid.org/0000-0001-8983-9539</orcidid></search><sort><creationdate>20190423</creationdate><title>Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-b0fece585e73e103790e22df37913858490ca4e06b77460375cffc6ddd342e483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Additives</topic><topic>Animals</topic><topic>Carbohydrate Conformation</topic><topic>Carbon</topic><topic>chemical compounds</topic><topic>chemical reactions</topic><topic>Clostridioides difficile - drug effects</topic><topic>Clostridioides difficile - metabolism</topic><topic>Clostridium difficile</topic><topic>Cosmetics</topic><topic>Degradation</topic><topic>Dose-Response Relationship, Drug</topic><topic>drugs</topic><topic>enzyme inhibitors</topic><topic>Epidemics</topic><topic>foods</topic><topic>human diseases</topic><topic>Human performance</topic><topic>microorganisms</topic><topic>Swine</topic><topic>therapeutics</topic><topic>trehalase</topic><topic>Trehalase - antagonists & inhibitors</topic><topic>Trehalase - metabolism</topic><topic>Trehalose</topic><topic>Trehalose - chemistry</topic><topic>Trehalose - metabolism</topic><topic>Trehalose - pharmacology</topic><topic>Virulence</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Danielson, Noah D</creatorcontrib><creatorcontrib>Collins, James</creatorcontrib><creatorcontrib>Stothard, Alicyn I</creatorcontrib><creatorcontrib>Dong, Qing Qing</creatorcontrib><creatorcontrib>Kalera, Karishma</creatorcontrib><creatorcontrib>Woodruff, Peter J</creatorcontrib><creatorcontrib>DeBosch, Brian J</creatorcontrib><creatorcontrib>Britton, Robert A</creatorcontrib><creatorcontrib>Swarts, Benjamin M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical communications (Cambridge, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Danielson, Noah D</au><au>Collins, James</au><au>Stothard, Alicyn I</au><au>Dong, Qing Qing</au><au>Kalera, Karishma</au><au>Woodruff, Peter J</au><au>DeBosch, Brian J</au><au>Britton, Robert A</au><au>Swarts, Benjamin M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile</atitle><jtitle>Chemical communications (Cambridge, England)</jtitle><addtitle>Chem Commun (Camb)</addtitle><date>2019-04-23</date><risdate>2019</risdate><volume>55</volume><issue>34</issue><spage>5009</spage><epage>5012</epage><pages>5009-5012</pages><issn>1359-7345</issn><issn>1364-548X</issn><eissn>1364-548X</eissn><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. 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| source | MEDLINE; Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Additives Animals Carbohydrate Conformation Carbon chemical compounds chemical reactions Clostridioides difficile - drug effects Clostridioides difficile - metabolism Clostridium difficile Cosmetics Degradation Dose-Response Relationship, Drug drugs enzyme inhibitors Epidemics foods human diseases Human performance microorganisms Swine therapeutics trehalase Trehalase - antagonists & inhibitors Trehalase - metabolism Trehalose Trehalose - chemistry Trehalose - metabolism Trehalose - pharmacology Virulence |
| title | Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile |
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