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-Structure paper
| Title | Human enterotoxigenic (ETEC) infections elicit antibodies that broadly neutralize mucinases of pathogenic and . |
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| Journal, issue, pages | Proc Natl Acad Sci U S A, Vol. 123, Issue 25, Page e2614012123, Year 2026 |
| Publish date | Jun 23, 2026 |
Authors | David P Buckley / Marjahan Akhtar / Mahima Thapa / Aaron Schmitz / Jackson Turner / Tim J Vickers / Nazia Khatoon / M Hasanul Kaisar / Jonathan A Coggin / Debayan Ganguli / Alaullah Sheikh / Renee M Laird / Frédéric Poly / Chad K Porter / Fernando Ruiz-Perez / Mark J Miller / Fahima Chowdhury / Tafiqur R Bhuiyan / Firdausi Qadri / Sergio Trillo-Muyo / Brendan Dolan / Sjoerd van der Post / Ali Ellebedy / Zachary T Berndsen / James M Fleckenstein / ![]() |
| PubMed Abstract | Enterotoxigenic (ETEC) and are the most common bacterial diarrheal pathogens among young children of low-middle income regions. Enteric pathogens must overcome formidable host defenses, including ...Enterotoxigenic (ETEC) and are the most common bacterial diarrheal pathogens among young children of low-middle income regions. Enteric pathogens must overcome formidable host defenses, including the protective barrier formed by intestinal mucus. ETEC produce a virulence protein called EatA, a member of the Serine Protease Autotransporter of the (SPATE) family, where the secreted passenger domain (EatA) specifically degrades MUC2, the major mucus secreted by goblet cells of the human intestine. Notably, some spp., as well as other diarrheagenic pathovars, secrete homologues of EatA known as SepA, and Pic. Here, we demonstrate that EatA, SepA, and Pic are functionally redundant MUC2 mucinases and that recombinant monoclonal antibodies (mAbs) derived from plasmablasts of ETEC-infected humans can inhibit MUC2 degradation by all three proteases. We present cryo-EM structures of EatA and the related SPATE proteins, SepA, and Pic, complexed to fragment antigen-binding portions of these mAbs to demonstrate that those targeting a core β-helix epitope shared by all three SPATE molecules broadly neutralize the capacity to degrade MUC2. These mAbs effectively prevent MUC2 degradation by each SPATE as well as mucus penetration by ETEC, , and Pic-producing enteroaggregative (EAEC). We anticipate that these studies could facilitate rational design of vaccines that broadly protect against major enteric pathogens by targeting a shared virulence feature. |
External links | Proc Natl Acad Sci U S A / PubMed:42296351 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 1.99 - 3.7 Å |
| Structure data | ![]() EMDB-73866: Raw consensus map of rEatAp complexed with Fab G12 ![]() EMDB-73867: Constituent EM map: local refinement of putative MUC2 binding domain of rEatAp and Fv domain of Fab G12 ![]() EMDB-73868: Constituent EM map: local refinement of putative MUC2 binding domain of rEatAp and Fab G12 from best Fab-containing 2D classes EMDB-73869, PDB-9z76: EMDB-73870, PDB-9z77: EMDB-73871, PDB-9z78: EMDB-73872, PDB-9z79: EMDB-73873, PDB-9z7a: EMDB-73874, PDB-9z7b: |
| Source |
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Keywords | HYDROLASE/IMMUNE SYSTEM / PROTEASE / BETA-HELIX / SECRETED / MONOCLONAL ANTIBODY / HYDROLASE / HYDROLASE-IMMUNE SYSTEM complex |
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homo sapiens (human)
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