Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera.
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 Esche...
Published in: | PLOS Neglected Tropical Diseases |
---|---|
Main Authors: | , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Public Library of Science (PLoS)
2018
|
Subjects: | |
Online Access: | https://doi.org/10.1371/journal.pntd.0006266 https://doaj.org/article/570ba0577a3544898a8a77fc9cc864c0 |
id |
ftdoajarticles:oai:doaj.org/article:570ba0577a3544898a8a77fc9cc864c0 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:570ba0577a3544898a8a77fc9cc864c0 2023-05-15T15:08:19+02:00 Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. Soumita Das Pavimol Angsantikul Christine Le Denny Bao Yukiko Miyamoto Weiwei Gao Liangfang Zhang Lars Eckmann 2018-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006266 https://doaj.org/article/570ba0577a3544898a8a77fc9cc864c0 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5839590?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006266 https://doaj.org/article/570ba0577a3544898a8a77fc9cc864c0 PLoS Neglected Tropical Diseases, Vol 12, Iss 2, p e0006266 (2018) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2018 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006266 2022-12-30T23:53:58Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 12 2 e0006266 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Soumita Das Pavimol Angsantikul Christine Le Denny Bao Yukiko Miyamoto Weiwei Gao Liangfang Zhang Lars Eckmann Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Soumita Das Pavimol Angsantikul Christine Le Denny Bao Yukiko Miyamoto Weiwei Gao Liangfang Zhang Lars Eckmann |
author_facet |
Soumita Das Pavimol Angsantikul Christine Le Denny Bao Yukiko Miyamoto Weiwei Gao Liangfang Zhang Lars Eckmann |
author_sort |
Soumita Das |
title |
Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. |
title_short |
Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. |
title_full |
Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. |
title_fullStr |
Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. |
title_full_unstemmed |
Neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. |
title_sort |
neutralization of cholera toxin with nanoparticle decoys for treatment of cholera. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2018 |
url |
https://doi.org/10.1371/journal.pntd.0006266 https://doaj.org/article/570ba0577a3544898a8a77fc9cc864c0 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 12, Iss 2, p e0006266 (2018) |
op_relation |
http://europepmc.org/articles/PMC5839590?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006266 https://doaj.org/article/570ba0577a3544898a8a77fc9cc864c0 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006266 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
12 |
container_issue |
2 |
container_start_page |
e0006266 |
_version_ |
1766339702850322432 |