Orally active bivalent VHH construct prevents proliferation of F4+ enterotoxigenic Escherichia coli in weaned piglets
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 104003 |
| Tidsskrift | iScience |
| Vol/bind | 25 |
| Udgave nummer | 4 |
| ISSN | 2589-0042 |
| DOI | |
| Status | Udgivet - 2022 |
| Eksternt udgivet | Ja |
Bibliografisk note
Funding Information:
We thank Innovation Fund Denmark (InnoBooster program, case number 7041-00260B ), and the Danish Ministry of Environment and Food Green Development and Demonstration Programme (GUDP) (case number 34009-19-1585 ) for financial support. We thank Louise Kruse Jensen (Department of Veterinary and Animal Sciences, Pathobiological Sciences) and her team for kindly donating pig tissue for this study. We thank DTU Proteomics Core for expert assistance in mass spectrometry analysis. We thank Inger Marie Jepsen, Aarhus University, Foulum, for her technical assistance in the in vivo ETEC challenge experiment with pigs and for cultivation and analysis of the E. coli in fecal samples of the pigs. We also thank Stine Lyngby, Technical University of Denmark, for her technical assistance with binding assays.
Funding Information:
We thank Innovation Fund Denmark (InnoBooster program, case number 7041-00260B), and the Danish Ministry of Environment and Food Green Development and Demonstration Programme (GUDP) (case number 34009-19-1585) for financial support. We thank Louise Kruse Jensen (Department of Veterinary and Animal Sciences, Pathobiological Sciences) and her team for kindly donating pig tissue for this study. We thank DTU Proteomics Core for expert assistance in mass spectrometry analysis. We thank Inger Marie Jepsen, Aarhus University, Foulum, for her technical assistance in the in vivo ETEC challenge experiment with pigs and for cultivation and analysis of the E. coli in fecal samples of the pigs. We also thank Stine Lyngby, Technical University of Denmark, for her technical assistance with binding assays. SWT and AHL designed the VHH constructs. LJ and GMH prepared DNA and genome sequenced ETEC isolates. SWT performed de novo assembly and genome analysis. BKF, SWT, SB, AHL, and CL designed the experiments. BKF, TK, SA, and LL performed the in vitro and ex vivo experiments, and CL performed the in vivo experiment. BKF, MP, TK, and SWT analyzed the data. BKF, MP, TK, SWT, CL, SB, and AHL wrote the manuscript. All authors revised and reviewed the manuscript. SWT and AHL are co-founders, employees, and shareholders in Bactolife ApS, and they are inventors behind the patent application WO2020144164A1. The authors declare no other conflicts of interest.
Publisher Copyright:
© 2022 The Author(s)
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