Characterization of the Antimicrobial Activities of Trichoplusia ni Cecropin A as a High-Potency Therapeutic against Colistin-Resistant Escherichia coli
Abstract
:1. Introduction
2. Materials and Methods
2.1. Peptide Synthesis
2.2. Bacteria Strains
2.3. Minimum Inhibitory Concentration (MIC)
2.4. Cytotoxicity
2.5. Hemolysis
2.6. Biofilm Inhibition Assay
2.7. Bacteria Outer Membrane Permeability Test
2.8. Circular Dichroism (CD) Analysis
2.9. Antimicrobial Activity Time-Course Assay
2.10. Bacteria Morphology Imaging
2.11. Limulus Amebocyte Lysate (LAL) Assay
2.12. BODIPY-TR-Cadaverine (BC) Displacement Assay
2.13. Isothermal Titration Calorimetry (ITC)
2.14. Saturation Transfer Difference (STD)-Nuclear Magnetic Resonance (NMR)
2.15. Suppression of LPS-Induced Inflammatory Cytokines
2.16. Suppression of Colistin-Resistant Bacteria-Induced Inflammatory Cytokines
2.17. Inhibition of Nitric Oxide (NO) Production by T. ni Cecropin in Response to Various Toll-like Receptors (TLRs)
2.18. Secreted Embryonic Alkaline Phosphatase (SEAP) Assay
2.19. Surface Plasmon Resonance (SPR)
2.20. Flow Cytometry
2.21. Animal Study Information
2.22. Mouse Model of LPS-Induced Endotoxemia
2.23. Histological Analysis of Lung Tissue
2.24. Data Analysis
3. Results
3.1. Antibacterial Activities of T. ni Cecropin
3.2. Toxicity of T. ni Cecropin to Mammalian Cells
3.3. T. ni Cecropin Inhibits ColREC Biofilm Formation
3.4. Antibacterial Mechanisms of T. ni Cecropin against Gram-Negative Bacteria
3.4.1. LPS-Neutralizing Capacity of T. ni Cecropin
3.4.2. Membrane Depolarization Ability of T. ni Cecropin against E. coli
3.4.3. T. ni Cecropin Induces E. coli Cell Membrane Damage
3.4.4. T. ni Cecropin Directly Interacts with LPS
3.4.5. Secondary Structure of T. ni Cecropin
3.5. Inhibition of Cytokine Production in RAW 264.7 Cells Stimulated by LPS or ColREC
3.6. T. ni Cecropin Selectively Targets the TLR4-Inflammatory Signaling Pathway
3.7. T. ni Cecropin Significantly Attenuates LPS-Induced Endotoxemia in a Mouse Model
4. Discussion
5. 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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Minimal Inhibitory Concentration (μM) | |||||
---|---|---|---|---|---|
Microorganism | Cecropin A | T. ni Cecropin | Polymyxin B | Colistin | Melittin |
E. coli | 2 | 2 | 0.25 | 0.25 | 8 |
A. baumannii | 2 | 1 | 0.5 | 0.25 | 4 |
P. aeruginosa | 8 | 4 | 2 | 1 | 32 |
K. pneumoniae | 1 | 1 | 0.25 | 0.25 | 32 |
ColREC 1557 | 1 | 1 | 8 | 8 | 2 |
ColREC 12 | 1 | 1 | 4 | 4 | 2 |
ColRAB 1915 | 1 | 1 | 64 | >64 | 2 |
ColRKP 139 | 2 | 2 | 64 | >64 | 32 |
GM * | 2.25 | 1.63 | 17.88 | 33.72 | 14.25 |
HC10 † | 200 | 200 | 200 | 200 | 3.1 |
Relative selective Index ** | 88.89 | 123.08 | 11.19 | 5.93 | 0.22 |
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Lee, H.; Kim, B.; Kim, M.; Yoo, S.; Lee, J.; Hwang, E.; Kim, Y. Characterization of the Antimicrobial Activities of Trichoplusia ni Cecropin A as a High-Potency Therapeutic against Colistin-Resistant Escherichia coli. Pharmaceutics 2023, 15, 1752. https://doi.org/10.3390/pharmaceutics15061752
Lee H, Kim B, Kim M, Yoo S, Lee J, Hwang E, Kim Y. Characterization of the Antimicrobial Activities of Trichoplusia ni Cecropin A as a High-Potency Therapeutic against Colistin-Resistant Escherichia coli. Pharmaceutics. 2023; 15(6):1752. https://doi.org/10.3390/pharmaceutics15061752
Chicago/Turabian StyleLee, Hyeju, Byeongkwon Kim, Minju Kim, Seoyeong Yoo, Jinkyeong Lee, Eunha Hwang, and Yangmee Kim. 2023. "Characterization of the Antimicrobial Activities of Trichoplusia ni Cecropin A as a High-Potency Therapeutic against Colistin-Resistant Escherichia coli" Pharmaceutics 15, no. 6: 1752. https://doi.org/10.3390/pharmaceutics15061752