From In Vitro Promise to In Vivo Reality: An Instructive Account of Infection Model Evaluation of Antimicrobial Peptides
Abstract
:1. Introduction
2. Results and Discussion
2.1. Peptides
2.2. Treatment with Ctn[15-34] Reduces Bacterial Levels in Females, Whereas Ctn re Does Not Improve the Survival Rate
2.3. Treatment with Ctn[15-34] Thrice a Day Lowers Bacterial Load but Does Not Improve Survival Rate
2.4. Ctn[15-34] Reduces Levels of TNF-α in Mice after 8 h and Ctn[15-34] re Increase TNF-α Levels in LPS-Stimulated Human MNC Cells
2.5. Organ Staining Consistent with Bacterial Levels at Each Treatment
3. Materials and Methods
3.1. Mice, Bacterial Strains and Other Material
3.2. Peptides
3.3. Minimum Inhibitory Concentration (MIC)
3.4. Peptide Cytotoxicity
3.5. Serum Stability
3.6. Tolerance in Mice
3.7. Mouse Systemic Infection
3.8. Efficacy in Mouse Infection Model
3.9. Evaluation of Body Weight and Clinical Symptoms
3.10. Evaluation of Colony-Forming Units (CFU) in Mouse Tissues
3.11. Quantification of TNF-α in Mouse Sera by ELISA
3.12. Stimulation of Human Mononuclear Cells (MNC) by LPS
3.13. Histopathology, Tissue Gram Stain and Hematoxylin and Eosin Stain
3.14. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Peptide | Sequence * | MIC (μM) A. baumannii | IC50 (μM) | t1/2 (min) |
---|---|---|---|---|
Ctn | KRFKKFFKKVKKSVKKRLKKIFKKPMVIGVTIPF | 0.78 | 14.32 | 71 |
Ctn re | fpitvGivmpkkfikklrkkvskkvkkffkkfrk | 1.56 | 4.3 | 211 |
Ctn[15-34] | KKRLKKIFKKPMVIGVTIPF | 0.78 | >100 | 770 |
Ctn[15-34] re | fpitvGivmpkkfikklrkk | 0.39 | 43 | 921 |
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Carrera-Aubesart, A.; Li, J.; Contreras, E.; Bello-Madruga, R.; Torrent, M.; Andreu, D. From In Vitro Promise to In Vivo Reality: An Instructive Account of Infection Model Evaluation of Antimicrobial Peptides. Int. J. Mol. Sci. 2024, 25, 9773. https://doi.org/10.3390/ijms25189773
Carrera-Aubesart A, Li J, Contreras E, Bello-Madruga R, Torrent M, Andreu D. From In Vitro Promise to In Vivo Reality: An Instructive Account of Infection Model Evaluation of Antimicrobial Peptides. International Journal of Molecular Sciences. 2024; 25(18):9773. https://doi.org/10.3390/ijms25189773
Chicago/Turabian StyleCarrera-Aubesart, Adam, Jiarui Li, Estefanía Contreras, Roberto Bello-Madruga, Marc Torrent, and David Andreu. 2024. "From In Vitro Promise to In Vivo Reality: An Instructive Account of Infection Model Evaluation of Antimicrobial Peptides" International Journal of Molecular Sciences 25, no. 18: 9773. https://doi.org/10.3390/ijms25189773