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Microbial Biotechnology Volume 12 ,Issue 1 ,2018-12-21
Synthetic consortia of nanobody‐coupled and formatted bacteria for prophylaxis and therapy interventions targeting microbiome dysbiosis‐associated diseases and co‐morbidities
Crystal Ball
Kenneth Timmis 1 James Kenneth Timmis 2 Harald Brüssow 3 Luis Ángel Fernández 4
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DOI:10.1111/1751-7915.13355
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摘要

Designed nanobody‐linked synthetic consortia for microbiota dysbiosis therapies. A. Nanobodies (Nb) are selected for specific antigens on target bacteria destined for a synthetic therapy consortium that may consist of two (B) or multiple (C) members. For the treatment of dysbiosis co‐morbidities requiring two functionally distinct consortia, these may be linked through a common member to generate a single bi‐functional microbiota therapy (D). image

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© 2019 John Wiley & Sons Ltd and Society for Applied Microbiology
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

图表

Nanobody display and synthetic adhesins of Escherichia coli. A. Structure of a camelid heavy chain‐only antibody (HCAb), indicating the constant Fc region and variable VHH domains. Nanobodies (Nbs) are the antigen‐binding VHH domains produced by engineered microbes.B. Surface display of Nbs on the E. coli cell surface, through their fusion to intimin N‐fragment 1‐654 comprising ß‐barrel and Ig‐like D0 domain, which anchors the Nb to the bacterial outer membrane (OM).

Designed nanobody‐linked synthetic consortia for microbiota dysbiosis therapies. A. Nanobodies (Nb) are selected for specific antigens on target bacteria destined for a synthetic therapy consortium that may consist of two (B) or multiple (C) members. For the treatment of dysbiosis co‐morbidities requiring two functionally distinct consortia, these may be linked through a common member to generate a single bi‐functional microbiota therapy (D).

Further potential therapeutic applications of synthetic consortia linked by surface‐displayed nanobodies. The figure portrays various interactions of synthetic consortia and the host microbiota and/or niches and tissue sites of the gastrointestinal tract mediating therapeutic activities. For instance, engineered bacterial strains in the consortia may deliver antigens or release biotherapeutics (e.g. antibodies, cytokines) locally to promote immune responses, e.g. in the Peyer's Patches, or reduce mucosal inflammation. Bacteria in the synthetic consortia may also display nanobodies to “trap” pathogens and kill them specifically by delivery of antibacterial toxins (e.g. microcins, effectors of type 6 secretion systems). These activities may favour colonization of the gastrointestinal tract by beneficial commensals during and after disease and dysbiosis. In addition, nanobody‐driven attachment of synthetic consortia to the mucosal surface may enhance therapeutic actions either favouring or preventing the absorption of specific metabolites by the host.

通讯作者

1. Kenneth Timmis.Institute of Microbiology, Technical University Braunschweig, Braunschweig, Germany.kntimmis@gmail.com
2. Luis Ángel Fernández.Department of Microbial Biotechnology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.kntimmis@gmail.com

推荐引用方式

Kenneth Timmis,James Kenneth Timmis,Harald Brüssow,Luis Ángel Fernández. Synthetic consortia of nanobody‐coupled and formatted bacteria for prophylaxis and therapy interventions targeting microbiome dysbiosis‐associated diseases and co‐morbidities. Microbial Biotechnology ,Vol.12, Issue 1(2018)

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