Diarrheal diseases are a major cause of morbidity and mortality worldwide. In many cases, antibiotic therapy is either ineffective or not recommended due to concerns about emergence of resistance. The pathogenesis of several of the most prevalent infections, including cholera and enteroxigenic Escherichia coli, is dominated by enterotoxins produced by lumen-dwelling pathogens before clearance by intestinal defenses. Toxins gain access to the host through critical host receptors, making these receptors attractive targets for alternative antimicrobial strategies that do not rely on conventional antibiotics. Here, we developed a new nanotechnology strategy as a countermeasure against cholera, one of the most important and prevalent toxin-mediated enteric infections. The key host receptor for cholera toxin, monosialotetrahexosylganglioside (GM1), was coated onto the surface of polymeric nanoparticles. The resulting GM1-polymer hybrid nanoparticles were shown to function as toxin decoys by selectively and stably binding cholera toxin, and neutralizing its actions on epithelial cells in vitro and in vivo. Furthermore, the GM1-coated nanoparticle decoys attenuated epithelial 3’,5’-cyclic adenosine monophosphate production and fluid responses to infection with live Vibrio cholera in cell culture and a murine infection model. Together, these studies illustrate that the new nanotechnology-based platform can be employed as a non-traditional antimicrobial strategy for the management of enteric infections with enterotoxin-producing pathogens.

腹泻病是全世界发病率和死亡率的主要原因。在许多情况下，由于担心产生耐药性，抗生素治疗要么无效要么不推荐使用。几种最普遍的感染的发病机理，包括霍乱和肠源性大肠杆菌肠毒素主要由腔内病原体产生的肠毒素在被肠道防御清除之前。毒素通过关键的宿主受体进入宿主，使这些受体成为不依赖常规抗生素的其他抗菌策略的有吸引力的靶标。在这里，我们开发了一种新的纳米技术策略来对抗霍乱，这是最重要，最普遍的毒素介导的肠道感染之一。霍乱毒素的关键宿主受体单唾液酸四己糖基神经节苷脂（GM1）被包被在聚合物纳米颗粒的表面上。结果显示，通过选择性和稳定地结合霍乱毒素，并在体外和体内中和其对上皮细胞的作用，所得的GM1聚合物杂化纳米颗粒起到了毒素诱饵的作用。。此外，涂有GM1的纳米颗粒诱饵减弱了细胞培养和小鼠感染模型中上皮3'，5'-环腺苷单磷酸的产生以及对活霍乱弧菌感染的流体反应。总之，这些研究表明，新的基于纳米技术的平台可以用作非传统抗微生物策略，用于管理产生肠毒素的病原体的肠道感染。