SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains and Media
2.2. Amino Acid Sequence Alignment and Phylogenetic Analysis
2.3. Cloning and Plasmids
2.4. Expression and Purification of Recombinant SP-1
2.5. Western Blotting and Kinetic Constant Determination
2.6. Peptide Library Preparation
2.7. Animals
2.8. Assessment of Mild Inflammation and Study Design
2.9. MPO Activity Measurement
2.10. Histological Evaluation and Scoring
2.11. Cell Cultures, SP-1 Treatment and Intestinal Permeability Assay
2.12. Cytokine Quantification
2.13. Fecal Protease Activity Measurement
2.14. Microbiota Analysis
2.15. Correlation Analyses
2.16. Statistical Analyses
3. Results
3.1. SP-1 Shares Conserved Sequence Features with Subtilisin Despite Overall Dissimilarity
3.2. Purification and Steady-State Kinetic Analysis of SP-1
3.3. Novel Substrate for SP-1
3.4. Administration of L. Lactis Secreting SP-1 Exacerbates DSS-Induced Colitis
3.5. SP-1 Increases Gut Inflammation and Fecal Protease Activity in Mice
3.6. Alteration of Gut Microbiota and Host Response
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
References
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Score | Weight Loss (%) | Stool Consistency | Visible Blood in Stool |
---|---|---|---|
0 | None | Normal | No bleeding |
1 | 1–5 | Loose stools | Slight bleeding |
2 | 5–10 | ||
3 | 10–15 | Diarrhea | Gross bleeding |
4 | >15 |
Substrate | Sequence |
---|---|
SP-1 | ABZ-Ileu-Met-Ala-Arg-ANB-NH2 |
Trypsin-like | AB2-Val-Val-Ser-Lys-ANB-NH2 |
Elastase-like | AB2-Met-Pro-Val-Ala-Trp-Glu-Tyr-(3-NO2)-NH2 |
PR3-like | AB2-Tyr-Tyr-ABU-Asn-Glu-Pro-Tyr-(3-NO2)-NH2 |
Substrate | KM × 10−4 (M) | kcat (s−1) | kcat/KM × 104 (M−1s−1) |
---|---|---|---|
ABZ-Ileu-Met-Ala-Arg-ANB-NH2 | 1.91 ± 0.3 | 2.83 ± 0.5 | 1.48 |
AB2-Val-Val-Ser-Lys-ANB-NH2 | 6.12 ± 0.5 | 1.79 ± 0.2 | 0.29 |
AB2-Met-Pro-Val-Ala-Trp-Glu-Tyr-(3-NO2)-NH2 | 17.7 ± 0.1 | 0.46 ± 0.08 | 0.025 |
AB2-Tyr-Tyr-ABU-Asn-Glu-Pro-Tyr-(3-NO2)-NH2 | 14.1 ± 0.7 | 0.40 ± 0.06 | 0.027 |
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Kriaa, A.; Jablaoui, A.; Rhimi, S.; Soussou, S.; Mkaouar, H.; Mariaule, V.; Gruba, N.; Gargouri, A.; Maguin, E.; Lesner, A.; et al. SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice. Cells 2021, 10, 2658. https://doi.org/10.3390/cells10102658
Kriaa A, Jablaoui A, Rhimi S, Soussou S, Mkaouar H, Mariaule V, Gruba N, Gargouri A, Maguin E, Lesner A, et al. SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice. Cells. 2021; 10(10):2658. https://doi.org/10.3390/cells10102658
Chicago/Turabian StyleKriaa, Aicha, Amin Jablaoui, Soufien Rhimi, Souha Soussou, Héla Mkaouar, Vincent Mariaule, Natalia Gruba, Ali Gargouri, Emmanuelle Maguin, Adam Lesner, and et al. 2021. "SP-1, a Serine Protease from the Gut Microbiota, Influences Colitis and Drives Intestinal Dysbiosis in Mice" Cells 10, no. 10: 2658. https://doi.org/10.3390/cells10102658