A molecular toolkit for heterologous protein secretion across Bacteroides species
Abstract Bacteroides species are abundant, prevalent, and stable members of the human gut microbiota, making them a promising chassis for developing long-term interventions for chronic diseases. Engineering Bacteroides as in situ bio-factories, however, requires efficient protein secretion tools, wh...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-53845-7 |
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| _version_ | 1832571520951517184 |
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| author | Yu-Hsuan Yeh Vince W. Kelly Rahman Rahman Pour Shannon J. Sirk |
| author_facet | Yu-Hsuan Yeh Vince W. Kelly Rahman Rahman Pour Shannon J. Sirk |
| author_sort | Yu-Hsuan Yeh |
| collection | DOAJ |
| description | Abstract Bacteroides species are abundant, prevalent, and stable members of the human gut microbiota, making them a promising chassis for developing long-term interventions for chronic diseases. Engineering Bacteroides as in situ bio-factories, however, requires efficient protein secretion tools, which are currently lacking. Here, we systematically investigate methods to enable heterologous protein secretion in Bacteroides. We identify a collection of secretion carriers that can export functional proteins across multiple Bacteroides species at high titers. To understand the mechanistic drivers of Bacteroides secretion, we characterize signal peptide sequence features, post-secretion extracellular fate, and the size limit of protein cargo. To increase titers and enable flexible control of protein secretion, we develop a strong, self-contained, inducible expression circuit. Finally, we validate the functionality of our secretion carriers in vivo in a mouse model. This toolkit promises to enable expanded development of long-term living therapeutic interventions for chronic gastrointestinal disease. |
| format | Article |
| id | doaj-art-6cf4f44b866d403d8e5332f68c577c32 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-6cf4f44b866d403d8e5332f68c577c322025-02-02T12:31:05ZengNature PortfolioNature Communications2041-17232024-11-0115111910.1038/s41467-024-53845-7A molecular toolkit for heterologous protein secretion across Bacteroides speciesYu-Hsuan Yeh0Vince W. Kelly1Rahman Rahman Pour2Shannon J. Sirk3Department of Bioengineering, University of Illinois Urbana-ChampaignDepartment of Bioengineering, University of Illinois Urbana-ChampaignDepartment of Bioengineering, University of Illinois Urbana-ChampaignDepartment of Bioengineering, University of Illinois Urbana-ChampaignAbstract Bacteroides species are abundant, prevalent, and stable members of the human gut microbiota, making them a promising chassis for developing long-term interventions for chronic diseases. Engineering Bacteroides as in situ bio-factories, however, requires efficient protein secretion tools, which are currently lacking. Here, we systematically investigate methods to enable heterologous protein secretion in Bacteroides. We identify a collection of secretion carriers that can export functional proteins across multiple Bacteroides species at high titers. To understand the mechanistic drivers of Bacteroides secretion, we characterize signal peptide sequence features, post-secretion extracellular fate, and the size limit of protein cargo. To increase titers and enable flexible control of protein secretion, we develop a strong, self-contained, inducible expression circuit. Finally, we validate the functionality of our secretion carriers in vivo in a mouse model. This toolkit promises to enable expanded development of long-term living therapeutic interventions for chronic gastrointestinal disease.https://doi.org/10.1038/s41467-024-53845-7 |
| spellingShingle | Yu-Hsuan Yeh Vince W. Kelly Rahman Rahman Pour Shannon J. Sirk A molecular toolkit for heterologous protein secretion across Bacteroides species Nature Communications |
| title | A molecular toolkit for heterologous protein secretion across Bacteroides species |
| title_full | A molecular toolkit for heterologous protein secretion across Bacteroides species |
| title_fullStr | A molecular toolkit for heterologous protein secretion across Bacteroides species |
| title_full_unstemmed | A molecular toolkit for heterologous protein secretion across Bacteroides species |
| title_short | A molecular toolkit for heterologous protein secretion across Bacteroides species |
| title_sort | molecular toolkit for heterologous protein secretion across bacteroides species |
| url | https://doi.org/10.1038/s41467-024-53845-7 |
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