PXD068558-1

PXD068558 is an original dataset announced via ProteomeXchange.

Title	Degradation of the intestinal mucus layer by the ETEC protease EatA is species specific determined by the structure of the MUC2 mucin
Description	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 facilitates access to the epithelial cell surface by degrading the core mucus component MUC2, thereby aiding to the 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 domains, which are uniquely spaced in human MUC2, contributing to species specificity. This was confirmed using a novel chimeric mouse model solely expressing human MUC2, which allowed us to study the role of the mucus layer in the infection of human intestinal pathogens. These findings highlight how ETEC has adapted to specifically degrade the mucus layer of its human host.
HostingRepository	PRIDE
AnnounceDate	2026-01-19
AnnouncementXML	Submission_2026-01-18_16:10:34.656.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	S.S van der Post
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Escherichia coli ETEC H10407; NCBI TaxID: NEWT:316401;
ModificationList	N-acetylhexosaminylated residue; monohydroxylated residue; Hex-HexNAc; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-09-19 03:26:28	ID requested
⏵ 1	2026-01-18 16:10:35	announced

Trillo-Muyo S, Dolan B, Svensson F, Vickers TJ, Arike L, Garc, í, a-Bonete MJ, Gustafsson JK, Nielsen MI, Wandall HH, Fleckenstein JM, Hansson GC, van der Post S, EatA mediated degradation of intestinal mucus is species-specific and driven by MUC2 structural features. Nat Commun, 17(1):158(2025) [pubmed]

10.1038/s41467-025-68037-0;

submitter keyword: Mucus, Mucin O-glycosylation, Protease, ETEC

Sjoerd van der Post
contact affiliation	Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Gothenburg, Sweden
contact email	sjoerd.van.der.post@medkem.gu.se
lab head
S.S van der Post
contact affiliation	Medical Chemistry
contact email	sjoerd.van.der.post@medkem.gu.se
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD068558
     1. Label: PRIDE project
     2. Name: Degradation of the intestinal mucus layer by the ETEC protease EatA is species specific determined by the structure of the MUC2 mucin