Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli
Abstract
:1. Introduction
2. Results
2.1. Antimicrobial Activity
2.2. Bacterial Membrane Permeabilization
2.3. Bacterial Killing Kinetics
2.4. Synergistic Effect with Vancomycin in the Presence of a Sub-Inhibitory Concentration (¼ ×MIC) of Peptides
2.5. Mechanism of Resensitization of Bacteria to Vancomycin by P-113 and its Derivatives
2.6. P-113 and its Derivatives Attenuate Vancomycin-Induced LPS Release
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Bacterial Strains and Culture Conditions
4.3. Serial Passage
4.4. Antimicrobial Activity Assay
4.5. Checkerboard Assay
4.6. Confocal Laser Scanning Microscopy
4.7. Calcein Leakage Assay
4.8. Time Killing Assay
4.9. Anti-Endotoxin Studies
4.10. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Name | Chemical Structure a | Sequence b | Molecular Weight (Da) |
---|---|---|---|
P-113 | Ac- A K R His His G Y K R K F His -NH2 | 1605.86 | |
Phe-P-113 | Ac- A K R Phe Phe G Y K R K F Phe -NH2 | 1635.99 | |
Bip-P-113 | Ac- A K R Bip Bip G Y K R K F Bip -NH2 | 1864.97 | |
Dip-P-113 | Ac- A K R Dip Dip G Y K R K F Dip -NH2 | 1864.06 | |
Nal-P-113 | Ac- A K R Nal Nal G Y K R K F Nal -NH2 | 1786.03 |
Bacterial Strains | MIC (μg/mL) | |||||
---|---|---|---|---|---|---|
Vancomycin | P-113 | Phe- P-113 | Bip- P-113 | Dip- P-113 | Nal- P-113 | |
E. faecium BCRC 15B0132 (VRE) | 64 | >64 | >64 | 4 | 4 | 4 |
Vancomycin-intermediate S. aureus 01 (VISA01) | 4 | >64 | >64 | 16 | 16 | 8 |
Vancomycin-intermediate S. aureus 02 (VISA02) | 4 | >64 | >64 | 16 | 16 | 8 |
Vancomycin-intermediate S. aureus 03 (VISA03) | 4 | >64 | >64 | 8 | 16 | 8 |
Vancomycin-resistant S. aureus 01 (VRSA01) | 32 | >64 | >64 | 16 | 32 | 8 |
Vancomycin-resistant S. aureus 02 (VRSA02) | 32 | >64 | >64 | 16 | 32 | 8 |
Vancomycin-resistant S. aureus 03 (VRSA03) | 32 | >64 | >64 | 8 | 32 | 16 |
E. coli ATCC 25922 | >64 | >64 | >64 | 32 | 64 | 32 |
Strains | AMP (μg/mL) (¼ ×MIC) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
P-113 | Phe-P-113 | Bip-P-113 | Dip-P-113 | Nal-P-113 | ||||||
VAN a | FICI b | VAN | FICI | VAN | FICI | VAN | FICI | VAN | FICI | |
VRE | 32 | 0.75 | 32 | 0.75 | 8 | 0.38 | 16 | 0.50 | 16 | 0.50 |
VISA 01 | 4 | 1.25 | 4 | 1.25 | 1 | 0.50 | 4 | 1.25 | 2 | 0.75 |
VISA 02 | 4 | 1.25 | 4 | 1.25 | 1 | 0.50 | 4 | 1.25 | 2 | 0.75 |
VISA 03 | 4 | 1.25 | 4 | 1.25 | 1 | 0.50 | 2 | 0.75 | 1 | 0.50 |
VRSA 01 | 32 | 1.25 | 32 | 1.25 | 2 | 0.31 | 16 | 0.75 | 8 | 0.50 |
VRSA 02 | 32 | 1.25 | 32 | 1.25 | 2 | 0.31 | 8 | 0.50 | 8 | 0.50 |
VRSA 03 | 32 | 1.25 | 32 | 1.25 | 4 | 0.38 | 16 | 0.75 | 4 | 0.38 |
E. coli ATCC 25922 | >64 | 1.25 | 64 | 0.75 | 16 | 0.38 | 32 | 0.50 | 16 | 0.38 |
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Wu, C.-L.; Hsueh, J.-Y.; Yip, B.-S.; Chih, Y.-H.; Peng, K.-L.; Cheng, J.-W. Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli. Int. J. Mol. Sci. 2020, 21, 4578. https://doi.org/10.3390/ijms21134578
Wu C-L, Hsueh J-Y, Yip B-S, Chih Y-H, Peng K-L, Cheng J-W. Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli. International Journal of Molecular Sciences. 2020; 21(13):4578. https://doi.org/10.3390/ijms21134578
Chicago/Turabian StyleWu, Chih-Lung, Ju-Yun Hsueh, Bak-Sau Yip, Ya-Han Chih, Kuang-Li Peng, and Jya-Wei Cheng. 2020. "Antimicrobial Peptides Display Strong Synergy with Vancomycin Against Vancomycin-Resistant E. faecium, S. aureus, and Wild-Type E. coli" International Journal of Molecular Sciences 21, no. 13: 4578. https://doi.org/10.3390/ijms21134578