SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice
Increased protease activity has been linked to the pathogenesis of IBD. While most studies have been focusing on host proteases in gut inflammation, it remains unclear how to address the potential contribution of their bacterial counterparts. In the present study, we report a functional characteriza...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/10/2658 |
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| author | Aicha Kriaa Amin Jablaoui Soufien Rhimi Souha Soussou Héla Mkaouar Vincent Mariaule Natalia Gruba Ali Gargouri Emmanuelle Maguin Adam Lesner Moez Rhimi |
| author_facet | Aicha Kriaa Amin Jablaoui Soufien Rhimi Souha Soussou Héla Mkaouar Vincent Mariaule Natalia Gruba Ali Gargouri Emmanuelle Maguin Adam Lesner Moez Rhimi |
| author_sort | Aicha Kriaa |
| collection | DOAJ |
| description | Increased protease activity has been linked to the pathogenesis of IBD. While most studies have been focusing on host proteases in gut inflammation, it remains unclear how to address the potential contribution of their bacterial counterparts. In the present study, we report a functional characterization of a newly identified serine protease, SP-1, from the human gut microbiota. The serine protease repertoire of gut <i>Clostridium</i> was first explored, and the specificity of SP-1 was analyzed using a combinatorial chemistry method. Combining in vitro analyses and a mouse model of colitis, we show that oral administration of recombinant bacteria secreting SP-1 (i) compromises the epithelial barrier, (ii) alters the microbial community, and (ii) exacerbates colitis. These findings suggest that gut microbial protease activity may constitute a valuable contributor to IBD and could, therefore, represent a promising target for the treatment of the disease. |
| first_indexed | 2024-03-10T06:39:31Z |
| format | Article |
| id | doaj.art-6c4d680de43040c79ff49c11dad51ad4 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:31Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6c4d680de43040c79ff49c11dad51ad42023-11-22T17:47:06ZengMDPI AGCells2073-44092021-10-011010265810.3390/cells10102658SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in MiceAicha Kriaa0Amin Jablaoui1Soufien Rhimi2Souha Soussou3Héla Mkaouar4Vincent Mariaule5Natalia Gruba6Ali Gargouri7Emmanuelle Maguin8Adam Lesner9Moez Rhimi10Microbiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceMicrobiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceMicrobiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceMicrobiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceMicrobiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceMicrobiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceFaculty of Chemistry, University of Gdansk, Uniwersytet Gdanski, Chemistry, Wita Stwosza 63, PL80-308 Gdansk, PolandLaboratory of Molecular Biotechnology of Eukaryotes, Center of Biotechnology of Sfax, University of Sfax, Sfax Bp ‘1177’ 3018, TunisiaMicrobiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceFaculty of Chemistry, University of Gdansk, Uniwersytet Gdanski, Chemistry, Wita Stwosza 63, PL80-308 Gdansk, PolandMicrobiota Interaction with Human and Animal Team (MIHA), Micalis Institute-UMR1319, AgroParisTech, Université Paris-Saclay, INRAE, F-78350 Jouy-en-Josas, FranceIncreased protease activity has been linked to the pathogenesis of IBD. While most studies have been focusing on host proteases in gut inflammation, it remains unclear how to address the potential contribution of their bacterial counterparts. In the present study, we report a functional characterization of a newly identified serine protease, SP-1, from the human gut microbiota. The serine protease repertoire of gut <i>Clostridium</i> was first explored, and the specificity of SP-1 was analyzed using a combinatorial chemistry method. Combining in vitro analyses and a mouse model of colitis, we show that oral administration of recombinant bacteria secreting SP-1 (i) compromises the epithelial barrier, (ii) alters the microbial community, and (ii) exacerbates colitis. These findings suggest that gut microbial protease activity may constitute a valuable contributor to IBD and could, therefore, represent a promising target for the treatment of the disease.https://www.mdpi.com/2073-4409/10/10/2658inflammatory bowel diseasesgut microbiotaserine proteasesmicrobiomeholobiont |
| spellingShingle | Aicha Kriaa Amin Jablaoui Soufien Rhimi Souha Soussou Héla Mkaouar Vincent Mariaule Natalia Gruba Ali Gargouri Emmanuelle Maguin Adam Lesner Moez Rhimi SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice Cells inflammatory bowel diseases gut microbiota serine proteases microbiome holobiont |
| title | SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice |
| title_full | SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice |
| title_fullStr | SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice |
| title_full_unstemmed | SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice |
| title_short | SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice |
| title_sort | sp 1 a serine protease from the gut microbiota influences colitis and drives intestinal dysbiosis in mice |
| topic | inflammatory bowel diseases gut microbiota serine proteases microbiome holobiont |
| url | https://www.mdpi.com/2073-4409/10/10/2658 |
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