Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning Diarrhea
Post-weaning diarrhea (PWD) and edema disease (ED), caused by enterotoxigenic and Shiga toxin producing <i>Escherichia coli</i> (ETEC and STEC) strains, are important diseases of newly weaned piglets worldwide. The objective of this study is to develop a passive immunization strategy to...
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| Format: | Article |
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MDPI AG
2021-02-01
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| Series: | Agriculture |
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| Online Access: | https://www.mdpi.com/2077-0472/11/3/186 |
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| author | Emmanuel Okello Kristof Moonens Joseph Erume Henri De Greve |
| author_facet | Emmanuel Okello Kristof Moonens Joseph Erume Henri De Greve |
| author_sort | Emmanuel Okello |
| collection | DOAJ |
| description | Post-weaning diarrhea (PWD) and edema disease (ED), caused by enterotoxigenic and Shiga toxin producing <i>Escherichia coli</i> (ETEC and STEC) strains, are important diseases of newly weaned piglets worldwide. The objective of this study is to develop a passive immunization strategy to protect piglets against PWD and ED using recombinant <i>Lactococcus lactis</i> added to piglet diet at weaning. The Variable Heavy chain domains of Heavy chain antibodies (VHHs) or Nanobodies (Nbs), directed against the fimbrial adhesins FaeG (F4 fimbriae) and FedF (F18 fimbriae) of <i>E. coli</i> were cloned and expressed on the surface of <i>L. lactis</i>. In vitro, the recombinant <i>L. lactis</i> strains agglutinated and inhibited adhesion of cognate F4 or F18 fimbriae expressing <i>E. coli</i> to pig villous preparation. In vivo, the anti-F4 <i>L. lactis</i> protected weaned piglets against a challenge with an F4-positive ETEC strain. Piglets supplemented with oral anti-F4 <i>L. lactis</i> showed reduced fecal <i>E. coli</i> shedding. We concluded that the surface expressed Nanobodies on <i>L. lactis</i> neutralized the adhesins of targeted <i>E. coli</i> and abrogated gut colonization, the first step in disease pathogenesis. As a proof of concept, we demonstrated the potential of passive immunization with recombinant <i>L. lactis</i> as a viable alternative to antibiotic prophylaxis in preventing piglet-post-weaning diarrhea. |
| first_indexed | 2024-03-09T00:35:56Z |
| format | Article |
| id | doaj.art-ddad14d6842f498d8eb4471f079258c8 |
| institution | Directory Open Access Journal |
| issn | 2077-0472 |
| language | English |
| last_indexed | 2024-03-09T00:35:56Z |
| publishDate | 2021-02-01 |
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| record_format | Article |
| series | Agriculture |
| spelling | doaj.art-ddad14d6842f498d8eb4471f079258c82023-12-11T18:13:04ZengMDPI AGAgriculture2077-04722021-02-0111318610.3390/agriculture11030186Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning DiarrheaEmmanuel Okello0Kristof Moonens1Joseph Erume2Henri De Greve3VIB-VUB Center for Structural Biology, Pleinlaan 2, 1050 Brussels, BelgiumVIB-VUB Center for Structural Biology, Pleinlaan 2, 1050 Brussels, BelgiumCollege of Veterinary Medicine, Animal Resources and Bio-security, Makerere University, P.O. Box 7062 Kampala, UgandaVIB-VUB Center for Structural Biology, Pleinlaan 2, 1050 Brussels, BelgiumPost-weaning diarrhea (PWD) and edema disease (ED), caused by enterotoxigenic and Shiga toxin producing <i>Escherichia coli</i> (ETEC and STEC) strains, are important diseases of newly weaned piglets worldwide. The objective of this study is to develop a passive immunization strategy to protect piglets against PWD and ED using recombinant <i>Lactococcus lactis</i> added to piglet diet at weaning. The Variable Heavy chain domains of Heavy chain antibodies (VHHs) or Nanobodies (Nbs), directed against the fimbrial adhesins FaeG (F4 fimbriae) and FedF (F18 fimbriae) of <i>E. coli</i> were cloned and expressed on the surface of <i>L. lactis</i>. In vitro, the recombinant <i>L. lactis</i> strains agglutinated and inhibited adhesion of cognate F4 or F18 fimbriae expressing <i>E. coli</i> to pig villous preparation. In vivo, the anti-F4 <i>L. lactis</i> protected weaned piglets against a challenge with an F4-positive ETEC strain. Piglets supplemented with oral anti-F4 <i>L. lactis</i> showed reduced fecal <i>E. coli</i> shedding. We concluded that the surface expressed Nanobodies on <i>L. lactis</i> neutralized the adhesins of targeted <i>E. coli</i> and abrogated gut colonization, the first step in disease pathogenesis. As a proof of concept, we demonstrated the potential of passive immunization with recombinant <i>L. lactis</i> as a viable alternative to antibiotic prophylaxis in preventing piglet-post-weaning diarrhea.https://www.mdpi.com/2077-0472/11/3/186post-weaning diarrheaedema diseasesETECSTECVHHNanobodies |
| spellingShingle | Emmanuel Okello Kristof Moonens Joseph Erume Henri De Greve Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning Diarrhea Agriculture post-weaning diarrhea edema diseases ETEC STEC VHH Nanobodies |
| title | Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning Diarrhea |
| title_full | Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning Diarrhea |
| title_fullStr | Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning Diarrhea |
| title_full_unstemmed | Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning Diarrhea |
| title_short | Orally Fed Recombinant <i>Lactococcus lactis</i> Displaying Surface Anti-Fimbrial Nanobodies Protects Piglets against <i>Escherichia coli</i> Causing Post-Weaning Diarrhea |
| title_sort | orally fed recombinant i lactococcus lactis i displaying surface anti fimbrial nanobodies protects piglets against i escherichia coli i causing post weaning diarrhea |
| topic | post-weaning diarrhea edema diseases ETEC STEC VHH Nanobodies |
| url | https://www.mdpi.com/2077-0472/11/3/186 |
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