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.