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EatA mediated degradation of intestinal mucus is species-specific and driven by MUC2 structural features
by
Svensson, Frida
, Fleckenstein, James M.
, Arike, Liisa
, Dolan, Brendan
, Trillo-Muyo, Sergio
, Nielsen, Mathias I.
, van der Post, Sjoerd
, Vickers, Tim J.
, Wandall, Hans H.
, García-Bonete, Maria-Jose
, Hansson, Gunnar C.
, Gustafsson, Jenny K.
in
14/19
/ 631/326/421
/ 631/45/468
/ 631/535/1267
/ 82/29
/ 82/58
/ 82/83
/ Adhesins
/ Animals
/ Bacteria
/ Bacterial diseases
/ Basic Medicine
/ Cell surface
/ Chemical bonds
/ Diarrhea
/ E coli
/ Enterotoxigenic Escherichia coli - metabolism
/ Enterotoxigenic Escherichia coli - pathogenicity
/ Epithelial cells
/ Epithelium
/ Escherichia coli
/ Escherichia coli Infections - metabolism
/ Escherichia coli Infections - microbiology
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Infections
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - microbiology
/ Intestine
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Mice, Transgenic
/ Mucin-2 - chemistry
/ Mucin-2 - genetics
/ Mucin-2 - metabolism
/ Mucus
/ Mucus - metabolism
/ multidisciplinary
/ Pathogenesis
/ Pathogens
/ Protease
/ Proteases
/ Proteinase
/ Proteins
/ Proteolysis
/ Science
/ Science (multidisciplinary)
/ Species Specificity
/ Toxins
/ Transgenic mice
/ Virulence
/ Virulence factors
2025
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EatA mediated degradation of intestinal mucus is species-specific and driven by MUC2 structural features
by
Svensson, Frida
, Fleckenstein, James M.
, Arike, Liisa
, Dolan, Brendan
, Trillo-Muyo, Sergio
, Nielsen, Mathias I.
, van der Post, Sjoerd
, Vickers, Tim J.
, Wandall, Hans H.
, García-Bonete, Maria-Jose
, Hansson, Gunnar C.
, Gustafsson, Jenny K.
in
14/19
/ 631/326/421
/ 631/45/468
/ 631/535/1267
/ 82/29
/ 82/58
/ 82/83
/ Adhesins
/ Animals
/ Bacteria
/ Bacterial diseases
/ Basic Medicine
/ Cell surface
/ Chemical bonds
/ Diarrhea
/ E coli
/ Enterotoxigenic Escherichia coli - metabolism
/ Enterotoxigenic Escherichia coli - pathogenicity
/ Epithelial cells
/ Epithelium
/ Escherichia coli
/ Escherichia coli Infections - metabolism
/ Escherichia coli Infections - microbiology
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Infections
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - microbiology
/ Intestine
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Mice, Transgenic
/ Mucin-2 - chemistry
/ Mucin-2 - genetics
/ Mucin-2 - metabolism
/ Mucus
/ Mucus - metabolism
/ multidisciplinary
/ Pathogenesis
/ Pathogens
/ Protease
/ Proteases
/ Proteinase
/ Proteins
/ Proteolysis
/ Science
/ Science (multidisciplinary)
/ Species Specificity
/ Toxins
/ Transgenic mice
/ Virulence
/ Virulence factors
2025
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EatA mediated degradation of intestinal mucus is species-specific and driven by MUC2 structural features
by
Svensson, Frida
, Fleckenstein, James M.
, Arike, Liisa
, Dolan, Brendan
, Trillo-Muyo, Sergio
, Nielsen, Mathias I.
, van der Post, Sjoerd
, Vickers, Tim J.
, Wandall, Hans H.
, García-Bonete, Maria-Jose
, Hansson, Gunnar C.
, Gustafsson, Jenny K.
in
14/19
/ 631/326/421
/ 631/45/468
/ 631/535/1267
/ 82/29
/ 82/58
/ 82/83
/ Adhesins
/ Animals
/ Bacteria
/ Bacterial diseases
/ Basic Medicine
/ Cell surface
/ Chemical bonds
/ Diarrhea
/ E coli
/ Enterotoxigenic Escherichia coli - metabolism
/ Enterotoxigenic Escherichia coli - pathogenicity
/ Epithelial cells
/ Epithelium
/ Escherichia coli
/ Escherichia coli Infections - metabolism
/ Escherichia coli Infections - microbiology
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Infections
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - microbiology
/ Intestine
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Mice, Transgenic
/ Mucin-2 - chemistry
/ Mucin-2 - genetics
/ Mucin-2 - metabolism
/ Mucus
/ Mucus - metabolism
/ multidisciplinary
/ Pathogenesis
/ Pathogens
/ Protease
/ Proteases
/ Proteinase
/ Proteins
/ Proteolysis
/ Science
/ Science (multidisciplinary)
/ Species Specificity
/ Toxins
/ Transgenic mice
/ Virulence
/ Virulence factors
2025
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EatA mediated degradation of intestinal mucus is species-specific and driven by MUC2 structural features
Journal Article
EatA mediated degradation of intestinal mucus is species-specific and driven by MUC2 structural features
2025
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Overview
Enterotoxigenic
Escherichia coli
(ETEC) infections are a leading cause of diarrheal illness, responsible for an estimated 100,000 deaths annually. ETEC pathogenesis is driven by various virulence factors, including toxins, adhesins, and noncanonical factors such as the protease EatA. The first line of host defense against intestinal pathogenic bacterial infections is the protective intestinal mucus layer. Here, we demonstrate the mechanism by which EatA degrades the core mucus component MUC2, thereby facilitating access to the epithelial cell surface and promoting infection. We identify the specific cleavage site region localized at the C-terminal of MUC2. EatA’s protease activity depends on the interaction between two distinct, uniquely spaced domains in human MUC2, which defines species specificity. We confirm this using a novel transgenic mouse model exclusively expressing human MUC2, which allows us to study the role of the mucus layer in the infection by human intestinal pathogens. These findings highlight how ETEC is adapted to specifically degrade the mucus layer of its human host.
In this work, authors show how the enterotoxigenic
Escherichia coli
(ETEC) protease EatA cleaves the human mucus protein MUC2 at a C-terminal site, allowing bacteria to cross the intestinal mucus, reach epithelial cells, and promote infection, as demonstrated using a human MUC2 transgenic mouse model.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 82/29
/ 82/58
/ 82/83
/ Adhesins
/ Animals
/ Bacteria
/ Diarrhea
/ E coli
/ Enterotoxigenic Escherichia coli - metabolism
/ Enterotoxigenic Escherichia coli - pathogenicity
/ Escherichia coli Infections - metabolism
/ Escherichia coli Infections - microbiology
/ Escherichia coli Proteins - genetics
/ Escherichia coli Proteins - metabolism
/ Humanities and Social Sciences
/ Humans
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - microbiology
/ Medicinska och farmaceutiska grundvetenskaper
/ Mice
/ Mucus
/ Protease
/ Proteins
/ Science
/ Toxins
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