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A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion
The enteric pathogen, Salmonella enterica is a major cause of human gastroenteritis globally and with increasing bacterial resistance to antibiotics, alternative solutions are urgently needed. Single domain antibodies (sdAbs), the smallest antibody fragments that retain antigen binding specificity a...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901939/ https://www.ncbi.nlm.nih.gov/pubmed/31849856 http://dx.doi.org/10.3389/fmicb.2019.02665 |
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author | Huen, Jennifer Yan, Zhun Iwashkiw, Jeremy Dubey, Shraddha Gimenez, Maria C. Ortiz, Maria E. Patel, Saumil V. Jones, Michael D. Riazi, Ali Terebiznik, Mauricio Babaei, Saeid Shahinas, Dea |
author_facet | Huen, Jennifer Yan, Zhun Iwashkiw, Jeremy Dubey, Shraddha Gimenez, Maria C. Ortiz, Maria E. Patel, Saumil V. Jones, Michael D. Riazi, Ali Terebiznik, Mauricio Babaei, Saeid Shahinas, Dea |
author_sort | Huen, Jennifer |
collection | PubMed |
description | The enteric pathogen, Salmonella enterica is a major cause of human gastroenteritis globally and with increasing bacterial resistance to antibiotics, alternative solutions are urgently needed. Single domain antibodies (sdAbs), the smallest antibody fragments that retain antigen binding specificity and affinity, are derived from variable heavy-chain only fragments (VHH) of camelid heavy-chain-only immunoglobulins. SdAbs typically contain a single disulfide bond simplifying recombinant protein production in microbial systems. These factors make sdAbs ideally suited for the development of effective anti-bacterial therapeutics. To this end, we generated an anti-Salmonella VHH library from which we screened for high affinity sdAbs. We present a novel sdAb (Abi-Se07) that targets the Salmonella virulence factor, FliC, required for bacterial motility and invasion of host cells. We demonstrate that Abi-Se07 bound FliC with a K(D) of 16.2 ± 0.1 nM. In addition, Abi-Se07 exhibited cross-serovar binding to whole cells of S. enterica serovar Typhimurium, Heidelberg, and Hadar. Abi-Se07 significantly inhibited bacterial motility and significantly reduced S. enterica colonization in a more native environment of chicken jejunum epithelium. Taken together, we have identified a novel anti-Salmonella sdAb and discuss future efforts toward therapeutic development. |
format | Online Article Text |
id | pubmed-6901939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69019392019-12-17 A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion Huen, Jennifer Yan, Zhun Iwashkiw, Jeremy Dubey, Shraddha Gimenez, Maria C. Ortiz, Maria E. Patel, Saumil V. Jones, Michael D. Riazi, Ali Terebiznik, Mauricio Babaei, Saeid Shahinas, Dea Front Microbiol Microbiology The enteric pathogen, Salmonella enterica is a major cause of human gastroenteritis globally and with increasing bacterial resistance to antibiotics, alternative solutions are urgently needed. Single domain antibodies (sdAbs), the smallest antibody fragments that retain antigen binding specificity and affinity, are derived from variable heavy-chain only fragments (VHH) of camelid heavy-chain-only immunoglobulins. SdAbs typically contain a single disulfide bond simplifying recombinant protein production in microbial systems. These factors make sdAbs ideally suited for the development of effective anti-bacterial therapeutics. To this end, we generated an anti-Salmonella VHH library from which we screened for high affinity sdAbs. We present a novel sdAb (Abi-Se07) that targets the Salmonella virulence factor, FliC, required for bacterial motility and invasion of host cells. We demonstrate that Abi-Se07 bound FliC with a K(D) of 16.2 ± 0.1 nM. In addition, Abi-Se07 exhibited cross-serovar binding to whole cells of S. enterica serovar Typhimurium, Heidelberg, and Hadar. Abi-Se07 significantly inhibited bacterial motility and significantly reduced S. enterica colonization in a more native environment of chicken jejunum epithelium. Taken together, we have identified a novel anti-Salmonella sdAb and discuss future efforts toward therapeutic development. Frontiers Media S.A. 2019-11-26 /pmc/articles/PMC6901939/ /pubmed/31849856 http://dx.doi.org/10.3389/fmicb.2019.02665 Text en Copyright © 2019 Huen, Yan, Iwashkiw, Dubey, Gimenez, Ortiz, Patel, Jones, Riazi, Terebiznik, Babaei and Shahinas. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Huen, Jennifer Yan, Zhun Iwashkiw, Jeremy Dubey, Shraddha Gimenez, Maria C. Ortiz, Maria E. Patel, Saumil V. Jones, Michael D. Riazi, Ali Terebiznik, Mauricio Babaei, Saeid Shahinas, Dea A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion |
title | A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion |
title_full | A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion |
title_fullStr | A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion |
title_full_unstemmed | A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion |
title_short | A Novel Single Domain Antibody Targeting FliC Flagellin of Salmonella enterica for Effective Inhibition of Host Cell Invasion |
title_sort | novel single domain antibody targeting flic flagellin of salmonella enterica for effective inhibition of host cell invasion |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901939/ https://www.ncbi.nlm.nih.gov/pubmed/31849856 http://dx.doi.org/10.3389/fmicb.2019.02665 |
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