Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera

PLoS Neglected Tropical Diseases
Soumita DasLars Eckmann

Abstract

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 re...Continue Reading

References

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Sep 1, 1999·Journal of Pediatric Gastroenterology and Nutrition·P I TarrM Donowitz

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Citations

Jan 10, 2019·The Journal of Infectious Diseases·Robert A FentonTimo Rieg
Aug 2, 2020·The Journal of Pharmacy and Pharmacology·Francisca B M SousaJand V R Medeiros
Jul 25, 2019·Frontiers in Pharmacology·Guoyu YangJianxiang Zhang
Oct 18, 2020·Vaccines·Giovanni GabuttiArmando Stefanati
Dec 11, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Adrija JhaSrinivas Mutalik
Jan 14, 2021·Nanomaterials·John Jairo Aguilera-CorreaMaría Vallet-Regí
Jan 11, 2019·Bioconjugate Chemistry·Diksha HaksarRoland J Pieters
Jul 3, 2019·ACS Applied Materials & Interfaces·Sarah BoesveldAlexander J C Kuehne
Nov 27, 2021·Advanced Healthcare Materials·Yonca KittelLaura De Laporte

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Methods Mentioned

BETA
nanoprecipitation
dynamic light scattering
fluorescence spectroscopy
fluorescence microscopy
ELISA
acetylation
Fluorescence imaging

Software Mentioned

GraphPad
Prism
GraphPad Prism

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