Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus
Abstract
:1. Introduction
2. Results
2.1. Antibacterial Assessment of Cyclic Peptides
2.2. Time-Kill Studies against MRSA
2.3. The Inhibition and Dispersal of Bacterial Biofilms
2.4. Persister Bacteria
2.5. Resistance Development
2.6. Safety Assessment
2.7. Membrane Permeabilization Studies
2.8. Combinational Activities against MRSA
3. Discussion
4. Materials and Methods
4.1. Cyclic Peptide-1, Cyclic Peptide-11, and Cyclic Peptide-14
4.2. Bacterial Strains and Growth Media
4.3. MIC and MBC Determinations
4.4. Time-Kill Curves
4.5. Inhibition of Biofilm Formation
4.6. Biofilm Dispersal
4.7. Antibacterial Properties against Persister Cells
4.8. Antibacterial Activities of Combinations against MRSA
4.9. Confocal Microscopy of Biofilms
4.10. Membrane Permeability Assay
4.11. Resistance Evolution Experiment
4.12. Hemolytic Assay
4.13. Cytotoxicity
4.14. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MIC | minimal inhibitory concentration |
MRS | methicillin-resistant Staphylococcus aureus |
EPS | extracellular polysaccharide |
MTT | methyl thiazolyltetrazolium |
PI | propidium iodide |
CFU | colony forming unit |
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MIC and MBC Test of Cyclic Peptide against Different MRSA Bacteria | ||||||||
---|---|---|---|---|---|---|---|---|
Compound | Value | MRSA 43300 | MRSA 3390 | MRSA 3392 | MRSA 3394 | MRSA 3396 | MRSA 3397 | MRSA 3398 |
cyclic peptide-1 | MIC (μM) | 5.1 | 5.1 | 5.1 | 5.1 | 5.1 | 5.1 | 5.1 |
MBC (μM) | 81.5 | 20.4 | 40.8 | 20.4 | 20.4 | 20.4 | 20.4 | |
cyclic peptide-11 | MIC (μM) | 10.6 | 10.6 | 10.6 | 10.6 | 10.6 | 10.6 | 10.6 |
MBC (μM) | 84.8 | 84.8 | 84.8 | 42.4 | 42.4 | 42.4 | 21.2 | |
cyclic peptide-14 | MIC (μM) | 10.6 | 10.6 | 10.6 | 10.6 | 10.6 | 10.6 | 10.6 |
MBC (μM) | 84.8 | 42.4 | 84.8 | 84.8 | 84.8 | 42.4 | 84.8 | |
vancomycin | MIC (μM) | 1.4 | 0.69 | 0.69 | 1.4 | 1.4 | 1.4 | 1.4 |
MBC (μM) | 2.8 | 1.4 | 1.4 | 2.8 | 2.8 | 2.8 | 2.8 |
MIC (μM) of Cyclic Peptides against ESKAPE Pathogen | ||||
---|---|---|---|---|
Compound | Cyclic Peptide-1 | Cyclic Peptide-11 | Cyclic Peptide-14 | |
Strains | ||||
Enterococcus faecium | >163 | >169.5 | >169.5 | |
Klebsiella pneumoniae | >163 | >169.5 | >169.5 | |
Acinetobacter baumannii | >163 | >169.5 | >169.5 | |
Pseudomonas aeruginosa | >163 | >169.5 | >169.5 | |
Enterobacter sp. | >163 | >169.5 | >169.5 |
Antibiotic Combinations | FICI Ratio |
---|---|
cyclic peptide-1–ciprofloxacin | 1 |
cyclic peptide-1–linezolid | 3 |
cyclic peptide-11–ciprofloxacin | 1 |
cyclic peptide-11–linezolid | 3 |
cyclic peptide-14–ciprofloxacin | 1 |
cyclic peptide-14–linezolid | 4 |
Compound | Structure |
---|---|
cyclic peptide-1 | |
cyclic peptide-11 | |
cyclic peptide-14 |
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Wei, G.; He, Y. Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus. Int. J. Mol. Sci. 2022, 23, 8029. https://doi.org/10.3390/ijms23148029
Wei G, He Y. Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus. International Journal of Molecular Sciences. 2022; 23(14):8029. https://doi.org/10.3390/ijms23148029
Chicago/Turabian StyleWei, Guoxing, and Yun He. 2022. "Antibacterial and Antibiofilm Activities of Novel Cyclic Peptides against Methicillin-Resistant Staphylococcus aureus" International Journal of Molecular Sciences 23, no. 14: 8029. https://doi.org/10.3390/ijms23148029