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Biocontainment strategies for in vivo applications of Saccharomyces boulardii

The human gastrointestinal tract is a complex and dynamic environment, playing a crucial role in human health. Microorganisms engineered to express a therapeutic activity have emerged as a novel modality to manage numerous diseases. Such advanced microbiome therapeutics (AMTs) must be contained with...

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Autores principales: Hedin, Karl Alex, Kruse, Vibeke, Vazquez-Uribe, Ruben, Sommer, Morten Otto Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986445/
https://www.ncbi.nlm.nih.gov/pubmed/36890914
http://dx.doi.org/10.3389/fbioe.2023.1136095
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author Hedin, Karl Alex
Kruse, Vibeke
Vazquez-Uribe, Ruben
Sommer, Morten Otto Alexander
author_facet Hedin, Karl Alex
Kruse, Vibeke
Vazquez-Uribe, Ruben
Sommer, Morten Otto Alexander
author_sort Hedin, Karl Alex
collection PubMed
description The human gastrointestinal tract is a complex and dynamic environment, playing a crucial role in human health. Microorganisms engineered to express a therapeutic activity have emerged as a novel modality to manage numerous diseases. Such advanced microbiome therapeutics (AMTs) must be contained within the treated individual. Hence safe and robust biocontainment strategies are required to prevent the proliferation of microbes outside the treated individual. Here we present the first biocontainment strategy for a probiotic yeast, demonstrating a multi-layered strategy combining an auxotrophic and environmental-sensitive strategy. We knocked out the genes THI6 and BTS1, causing thiamine auxotrophy and increased sensitivity to cold, respectively. The biocontained Saccharomyces boulardii showed restricted growth in the absence of thiamine above 1 ng/ml and exhibited a severe growth defect at temperatures below 20°C. The biocontained strain was well tolerated and viable in mice and demonstrated equal efficiency in peptide production as the ancestral non-biocontained strain. In combination, the data support that thi6∆ and bts1∆ enable biocontainment of S. boulardii, which could be a relevant chassis for future yeast-based AMTs.
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spelling pubmed-99864452023-03-07 Biocontainment strategies for in vivo applications of Saccharomyces boulardii Hedin, Karl Alex Kruse, Vibeke Vazquez-Uribe, Ruben Sommer, Morten Otto Alexander Front Bioeng Biotechnol Bioengineering and Biotechnology The human gastrointestinal tract is a complex and dynamic environment, playing a crucial role in human health. Microorganisms engineered to express a therapeutic activity have emerged as a novel modality to manage numerous diseases. Such advanced microbiome therapeutics (AMTs) must be contained within the treated individual. Hence safe and robust biocontainment strategies are required to prevent the proliferation of microbes outside the treated individual. Here we present the first biocontainment strategy for a probiotic yeast, demonstrating a multi-layered strategy combining an auxotrophic and environmental-sensitive strategy. We knocked out the genes THI6 and BTS1, causing thiamine auxotrophy and increased sensitivity to cold, respectively. The biocontained Saccharomyces boulardii showed restricted growth in the absence of thiamine above 1 ng/ml and exhibited a severe growth defect at temperatures below 20°C. The biocontained strain was well tolerated and viable in mice and demonstrated equal efficiency in peptide production as the ancestral non-biocontained strain. In combination, the data support that thi6∆ and bts1∆ enable biocontainment of S. boulardii, which could be a relevant chassis for future yeast-based AMTs. Frontiers Media S.A. 2023-02-20 /pmc/articles/PMC9986445/ /pubmed/36890914 http://dx.doi.org/10.3389/fbioe.2023.1136095 Text en Copyright © 2023 Hedin, Kruse, Vazquez-Uribe and Sommer. https://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 Bioengineering and Biotechnology
Hedin, Karl Alex
Kruse, Vibeke
Vazquez-Uribe, Ruben
Sommer, Morten Otto Alexander
Biocontainment strategies for in vivo applications of Saccharomyces boulardii
title Biocontainment strategies for in vivo applications of Saccharomyces boulardii
title_full Biocontainment strategies for in vivo applications of Saccharomyces boulardii
title_fullStr Biocontainment strategies for in vivo applications of Saccharomyces boulardii
title_full_unstemmed Biocontainment strategies for in vivo applications of Saccharomyces boulardii
title_short Biocontainment strategies for in vivo applications of Saccharomyces boulardii
title_sort biocontainment strategies for in vivo applications of saccharomyces boulardii
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9986445/
https://www.ncbi.nlm.nih.gov/pubmed/36890914
http://dx.doi.org/10.3389/fbioe.2023.1136095
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