State Key Laboratory of Food Science and Resources, Jiangnan University, Wuxi 214122, China.
School of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
J Agric Food Chem. 2024 Oct 23;72(42):23533-23543. doi: 10.1021/acs.jafc.4c07612. Epub 2024 Oct 10.
Bacterial infections have been seriously endangering public health and life, making it imperative to explore novel anti-infection strategies for their control. Herein, we constructed a DNA hydrogel encoded with aptamers (Apt-hydrogel) to inhibit Shiga toxin II (Stx2) toxicity, thereby alleviating (EHEC) infection. The Apt-hydrogel was formed by two Y-shaped DNA scaffolds through rational design, where one end of Y was encoded with an aptamer sequence targeting the B subunit of Shiga toxin II (Stx2B). The Apt-hydrogel not only retained the high affinity of the aptamer but also provided protection for the aptamer, endowing it with better stability and biocompatibility. The results from in vitro and in vivo demonstrated good mediation effects of the Apt-hydrogel on Stx2 toxicity and confirmed its excellent inhibition activity. We hypothesized that the mechanism could be attributed to the high affinity of Apt-hydrogel for Stx2B, which effectively occupies the active site of Stx2B and its receptor Gb3. This interaction enhanced steric hindrance, thereby mediating their interaction and preventing Stx2 from entering the cell to exert toxicity. We anticipate that the novel Apt-hydrogel will expand the usage of aptamers and provide a new dimension for the Apt-hydrogel as a promising blocking assistant to inhibit Shiga toxin infections via a strong steric hindrance effect.
细菌感染严重威胁着公众健康和生命，因此必须探索新的抗感染策略来控制它们。在这里，我们构建了一种编码适体的 DNA 水凝胶（Apt-hydrogel），以抑制志贺毒素 II（Stx2）的毒性，从而缓解肠出血性大肠杆菌（EHEC）感染。Apt-hydrogel 通过合理设计由两个 Y 形 DNA 支架形成，其中 Y 的一端编码针对 Shiga 毒素 II（Stx2B）B 亚基的适体序列。Apt-hydrogel 不仅保留了适体的高亲和力，而且为适体提供了保护，赋予其更好的稳定性和生物相容性。体外和体内的结果表明，Apt-hydrogel 对 Stx2 毒性具有良好的介导作用，并证实了其优异的抑制活性。我们假设其机制可能归因于 Apt-hydrogel 与 Stx2B 的高亲和力，有效地占据了 Stx2B 及其受体 Gb3 的活性位点。这种相互作用增强了空间位阻，从而介导它们的相互作用，并防止 Stx2 进入细胞发挥毒性。我们预计，新型 Apt-hydrogel 将扩大适体的用途，并为 Apt-hydrogel 作为一种有前途的阻断辅助物通过强大的空间位阻效应抑制志贺毒素感染提供新的维度。
