EatA mediated degradation of intestinal mucus is species-specific and driven by MUC2 structural features
Year: 2025
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Veterans Affairs, Lundbeckfonden, Stiftelserna Wilhelm och Martina Lundgrens, Svenska Sällskapet för Medicinsk Forskning, Vetenskapsrådet, Sahlgrenska Universitetssjukhuset, Göteborgs Universitet, Magnus Bergvalls Stiftelse, Harald och Greta Jeanssons Stiftelse, H. Lundbeck A/S, National Institutes of Health, Horizon 2020 Framework Programme, National Institute of Allergy and Infectious Diseases, HORIZON EUROPE European Research Council
Awards: G1297504306, Molecular Pathogenesis of Enterotoxigenic Escherichia coli Infections, Molecular Microbiology of Enterotoxigenic E. coli Pathogen-Host Interactions, G2122880468, Regulation of colonic stem cell proliferation: A novel role for redox signaling, G4270338735, G7379863885, G7771828741, G8152750745, G8235638645, G8339405863, G8743140301, G890636787, Novel Antigen Identification for an enterotoxigenic E coli vaccine, Novel treatments for the mucus accumulation at chronic lung diseases
OpenAlex ID: W7117780168