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DTU Findit

Journal article

Orally active bivalent VHH construct prevents proliferation of F4+ enterotoxigenic Escherichia coli in weaned piglets

From

Technical University of Denmark1

Infection Microbiology, Section for Microbial and Chemical Ecology, Department of Biotechnology and Biomedicine, Technical University of Denmark2

Center for Microbial Secondary Metabolites, Centers, Technical University of Denmark3

Aarhus University4

Disease Systems Immunology, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark5

Bactolife ApS6

Department of Biotechnology and Biomedicine, Technical University of Denmark7

Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark8

Protein Glycoscience and Biotechnology, Section for Protein Chemistry and Enzyme Technology, Department of Biotechnology and Biomedicine, Technical University of Denmark9

DTU Microbes Initiative, Centers, Technical University of Denmark10

Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark11

Tropical Pharmacology and Biotherapeutics, Section for Protein Science and Biotherapeutics, Department of Biotechnology and Biomedicine, Technical University of Denmark12

Section for Microbial and Chemical Ecology, Department of Biotechnology and Biomedicine, Technical University of Denmark13

...and 3 more

A major challenge in industrial pig production is the prevalence of post-weaning diarrhea (PWD) in piglets, often caused by enterotoxigenic Escherichia coli (ETEC). The increased use of antibiotics and zinc oxide to treat PWD has raised global concerns regarding antimicrobial resistance development and environmental pollution.

Still, alternative treatments targeting ETEC and counteracting PWD are largely lacking. Here, we report the design of a pH, temperature, and protease-stable bivalent VHH-based protein BL1.2 that cross-links a F4+ ETEC model strain by selectively binding to its fimbriae. This protein inhibits F4+ ETEC adhesion to porcine epithelial cells ex vivo and decreases F4+ ETEC proliferation when administrated as a feed additive to weaned F4+ ETEC challenged piglets.

These findings highlight the potential of a highly specific bivalent VHH-based feed additive in effectively delimiting pathogenic F4+ ETEC bacteria proliferation in piglets and may represent a sustainable solution for managing PWD while circumventing antimicrobial resistance development.

Language: English
Publisher: Elsevier
Year: 2022
Pages: 104003
ISSN: 25890042
Types: Journal article
DOI: 10.1016/j.isci.2022.104003
ORCIDs: Pichler, Michael , Ledsgaard, Line , Ahmadi, Shirin , Hermansen, Grith Miriam Maigaard , Jelsbak, Lars , Brix, Susanne and Laustsen, Andreas Hougaard

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