抗降解海藻糖类似物可阻止产毒艰难梭菌利用海藻糖。
Degradation-resistant trehalose analogues block utilization of trehalose by hypervirulent Clostridioides difficile.
机构信息
Department of Chemistry and Biochemistry, Central Michigan University, Mount Pleasant, MI, USA.
出版信息
Chem Commun (Camb). 2019 Apr 23;55(34):5009-5012. doi: 10.1039/c9cc01300h.
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.
摘要
海藻糖被用作数千种食品、化妆品和药品的添加剂，并且作为多种人类疾病的治疗药物正在被研究。然而，其作为微生物碳源的能力是一个关注点，最近的发现强调了这一点，即海藻糖可以被流行的艰难梭菌代谢并可能增强其毒力。在这里，我们表明，设计用于抵抗酶降解的海藻糖类似物不能被艰难梭菌用作碳源。此外，我们证明，海藻糖类似物而不是已知的海藻糖酶抑制剂 validamycin A 能够抑制高毒力艰难梭菌的天然海藻糖利用。因此，抗降解的海藻糖类似物可用作海藻糖酶抑制剂，并且在酶促分解是关注点的应用中，作为海藻糖的替代品或与海藻糖共同添加物。
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