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Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment
Francisella tularensis (Ft), the causative agent of lethal tularemia, is classified as a category A biological warfare threat agent. While Ft infection is treatable by antibiotics, many failed antibiotic treatments were reported, highlighting the need for effective new treatments. It has been demons...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684794/ https://www.ncbi.nlm.nih.gov/pubmed/31388083 http://dx.doi.org/10.1038/s41598-019-47931-w |
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author | Mechaly, Adva Elia, Uri Alcalay, Ron Cohen, Hila Epstein, Eyal Cohen, Ofer Mazor, Ohad |
author_facet | Mechaly, Adva Elia, Uri Alcalay, Ron Cohen, Hila Epstein, Eyal Cohen, Ofer Mazor, Ohad |
author_sort | Mechaly, Adva |
collection | PubMed |
description | Francisella tularensis (Ft), the causative agent of lethal tularemia, is classified as a category A biological warfare threat agent. While Ft infection is treatable by antibiotics, many failed antibiotic treatments were reported, highlighting the need for effective new treatments. It has been demonstrated that binding of antibody-coated bacteria to the Fc receptor located on phagocytic cells is a key process needed for efficient protection against Ft. Yet, Ft utilizes the same receptor to enter the phagocytic cells in order to escape the immune system. To address the question whether an anti-Ft LPS antibody lacking the ability to bind the Fc receptor may inhibit the entry of Ft into host cells, a soluble scFv (TL1-scFv) was constructed from an anti Ft-LPS antibody (TL1) that was isolated from an immune single-chain (scFv) phage-display library. Bacterial uptake was assessed upon infection of macrophages with Ft live attenuated strain (LVS) in the presence of either TL1 or TL1-scFv. While incubation of LVS in the presence of TL1 greatly enhanced bacterial uptake, LVS uptake was significantly inhibited in the presence of TL1-scFv. These results prompt further experiments probing the therapeutic efficacy of TL1-scFv, alone or in combination with antibiotic treatment. |
format | Online Article Text |
id | pubmed-6684794 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-66847942019-08-11 Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment Mechaly, Adva Elia, Uri Alcalay, Ron Cohen, Hila Epstein, Eyal Cohen, Ofer Mazor, Ohad Sci Rep Article Francisella tularensis (Ft), the causative agent of lethal tularemia, is classified as a category A biological warfare threat agent. While Ft infection is treatable by antibiotics, many failed antibiotic treatments were reported, highlighting the need for effective new treatments. It has been demonstrated that binding of antibody-coated bacteria to the Fc receptor located on phagocytic cells is a key process needed for efficient protection against Ft. Yet, Ft utilizes the same receptor to enter the phagocytic cells in order to escape the immune system. To address the question whether an anti-Ft LPS antibody lacking the ability to bind the Fc receptor may inhibit the entry of Ft into host cells, a soluble scFv (TL1-scFv) was constructed from an anti Ft-LPS antibody (TL1) that was isolated from an immune single-chain (scFv) phage-display library. Bacterial uptake was assessed upon infection of macrophages with Ft live attenuated strain (LVS) in the presence of either TL1 or TL1-scFv. While incubation of LVS in the presence of TL1 greatly enhanced bacterial uptake, LVS uptake was significantly inhibited in the presence of TL1-scFv. These results prompt further experiments probing the therapeutic efficacy of TL1-scFv, alone or in combination with antibiotic treatment. Nature Publishing Group UK 2019-08-06 /pmc/articles/PMC6684794/ /pubmed/31388083 http://dx.doi.org/10.1038/s41598-019-47931-w Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mechaly, Adva Elia, Uri Alcalay, Ron Cohen, Hila Epstein, Eyal Cohen, Ofer Mazor, Ohad Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment |
title | Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment |
title_full | Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment |
title_fullStr | Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment |
title_full_unstemmed | Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment |
title_short | Inhibition of Francisella tularensis phagocytosis using a novel anti-LPS scFv antibody fragment |
title_sort | inhibition of francisella tularensis phagocytosis using a novel anti-lps scfv antibody fragment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684794/ https://www.ncbi.nlm.nih.gov/pubmed/31388083 http://dx.doi.org/10.1038/s41598-019-47931-w |
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