Post-weaning diarrhea (PWD) is a major health problem in weaned piglets and is associated with impaired growth performance and production efficiency. Enterotoxigenic Escherichia coli (ETEC) is an important pathogen involved in PWD, with bacterial adhesion and enterotoxin activity being key mechanisms of pathogenesis. Although antibiotics and medicinal zinc oxide have traditionally been used for PWD control, concerns regarding antimicrobial resistance (AMR) and environmental impacts have increased interest in targeted non-antibiotic strategies. Recent studies have explored VHH-based specific binding proteins for ETEC control, with single-domain antibodies (VHHs) attracting attention because of their ability to specifically recognize bacterial virulence factors. An earlier study demonstrated that the bivalent VHH-based protein BL1.2 specifically binds F4 fimbriae, inhibits F4⁺ ETEC adhesion to porcine intestinal epithelial cells, and reduces F4⁺ ETEC proliferation in challenged weaned piglets. Building on this single-virulence-factor targeting strategy, a subsequent study developed BL2.2, targeting the B-subunit of heat-labile enterotoxin (LT), and evaluated BL1.2 and BL2.2 as a combined feed additive to target bacterial adhesion and toxin activity. The two constructs specifically bound their respective virulence factors without affecting bacterial growth in vitro, while oral administration after ETEC challenge reduced F4⁺ ETEC proliferation and was associated with earlier enrichment of bacterial groups related to a more mature gut microbiota. Overall, VHH-based specific binding proteins show potential as a targeted non-antibiotic strategy for ETEC control, with research progressing from targeting a single virulence factor toward addressing multiple mechanisms of ETEC pathogenicity and potentially contributing to the prevention of ETEC-related PWD.
- Fiil, B. K., S. W. Thrane, M. Pichler, T. Kittilä, L. Ledsgaard, S. Ahmadi, G. M. M. Hermansen, L. Jelsbak, C. Lauridsen, S. Brix, and A. H. Laustsen. 2022. Orally active bivalent VHH construct prevents proliferation of F4+ enterotoxigenic Escherichia coli in weaned piglets. iScience 25:104003. doi:10.1016/j.isci.2022.104003.
- Jenkins, T. P., N. Ács, E. W. Arendrup, A. Swift, Á. Duzs, I. Chatzigiannidou, M. Pichler, T. Kittilä, L. Peachey, L. Gram, N. Canibe, A. H. Laustsen, S. Brix, and S. W. Thrane. 2024. Protecting the piglet gut microbiota against ETEC-mediated post-weaning diarrhoea using specific binding proteins. npj Biofilms Microbiomes 10:42. doi:10.1038/s41522-024-00514-8.
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