The Antimicrobial, Antibiofilm and Anti-Inflammatory Activities of P13#1, a Cathelicidin-like Achiral Peptoid
Abstract
:1. Introduction
2. Results and Discussion
2.1. The Design of Peptoid P13#1
2.2. Synthesis of P13#1
2.3. The Antimicrobial Activity of P13#1
2.4. Peptoid–Antibiotic Interaction Study
2.5. The Anti-Biofilm Activity of P13#1
2.6. Interactions of P13#1 with SDS, LPSs and Bacterial Cells
2.7. The Anti-Inflammatory Activity of P13#1 in Cell Cultures
2.8. The In Vivo Efficacy of P13#1
3. Materials and Methods
3.1. Materials and General Methods
3.2. Solid-Phase Synthesis of P13#1
3.3. Solid-Phase Synthesis of CG-P13#1
3.4. Conformational Analysis of P13#1
3.5. The Purification of P13#1
3.6. The Preparation of the Labeled Peptoids
3.7. The Production and Labelling of the Recombinant Peptides
3.8. Antimicrobial Assay
3.9. Anti-Biofilm Assay
3.10. The Interaction of Labeled Species with LPSs and SDS
3.11. The Interaction of the Labeled Species with Bacterial Cells
3.12. KD Calues and Binding Stoichiometries toward LPS
3.13. MTT Assay
3.14. The Immune-Modulatory Activity of P13#1
3.15. In Vivo Assays
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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MIC (MBC) 1 | MIC | |||
---|---|---|---|---|
(μM) | (μM) | |||
Bacterial Strain | P13#1 | (P)GKY20 | Vanc 2 | Pol B 2 |
Gram(−) | ||||
Pseudomonas aeruginosa PAO1 | 1.56 (1.56) | 3.12 (3.12) | 0.18 | |
Pseudomonas aeruginosa KK27 | 1.56 (1.56) | nd 3 | 0.36 | |
Pseudomonas aeruginosa RP73 | 1.56 (1.56) | 1.56 (1.56) | 0.09 | |
Pseudomonas aeruginosa AA2 | 1.56 (1.56) | nd | 0.36 | |
Pseudomonas aeruginosa PA14 | 1.56 (1.56) | 6.25 (6.25) | 0.18 | |
Klebsiella pneumoniae ATCC 700603 | 1.56 (1.56) | 6.25 (6.25) | 0.36 | |
Acinetobacter baumanii ATCC 17878 | 1.56 (1.56) | 3.12 (3.12) | 0.18 | |
Burkholderia cenocepacea LMG 18863 | >50 | >50 | >46.2 | |
Escherichia coli ATCC 25922 | 1.56 (1.56) | 6.25 (6.25) | 0.72 | |
Salmonella typhimurium ATCC 14028 | 1.56 (1.56) | 3.12 (3.12) | 0.36 | |
Salmonella enteriditis 706 RIVM | 1.56 (1.56) | 6.25 (6.25) | 0.72 | |
Gram(+) | ||||
Staphylococcus aureus ATCC 6538P | 0.78 (0.78) | 1.56 (1.56) | 0.34 | |
Staphylococcus aureus WKZ2 (MRSA) | 1.56 (1.56) | nd | 0.34 | |
Staphylococcus aureus Newman | 3.12 (3.12) | 6.25 (6.25) | 0.17 | |
Enterococcus faecalis ATCC 29212 | 1.56 (1.56) | 1.56 (1.56) | 0.34 |
Bacterial Strains | Antibiotic | MIC (μg/mL) | ΣFICi 1 |
---|---|---|---|
P13#1 | |||
Gram(−) | |||
Pseudomonas aeruginosa PAO1 | Tobramycin | 0.0078 | 0.626 |
Ciprofloxacin | 0.125 | 0.750 | |
Colistin | 0.25 | 0.376 | |
Meropenem | 0.25 | 2 | |
Gram(+) | |||
Staphylococcus aureus ATCC 6538P | Tobramycin | 0.00097 | 0.750 |
Ciprofloxacin | 0.125 | 1 | |
Meropenem | 0.0625 | 2 |
Peptide/ Peptoid | LPSEc 1 (µg/mL) | KD (µM) | [Binding Sites] (µM) | Stoichiometry 2 (Peptoid:LPS) |
---|---|---|---|---|
Luc-P13#1 | 40 | 0.121 (±0.032) | 4.53 (±0.123) | 1.13:1 |
Luc-P13#1 | 5 | 0.085 (±0.021) | 2.21 (±0.107) | 4.42:1 |
Luc-GKY20 | 40 | 0.382 (±0.030) | 6.12 (±0.109) | 1.53:1 |
Luc-GKY20 | 5 | 0.109 (±0.022) | 2.62 (±0.153) | 5.24:1 |
LPSPa 3 (µg/mL) | ||||
Luc-P13#1 | 5 | 0.032 (±0.0085) | 1.91 (±0.049) | - |
Luc-GKY20 | 5 | 0.054 (±0.013) | 2.1 (±0.08) | - |
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Cafaro, V.; Bosso, A.; Di Nardo, I.; D’Amato, A.; Izzo, I.; De Riccardis, F.; Siepi, M.; Culurciello, R.; D’Urzo, N.; Chiarot, E.; et al. The Antimicrobial, Antibiofilm and Anti-Inflammatory Activities of P13#1, a Cathelicidin-like Achiral Peptoid. Pharmaceuticals 2023, 16, 1386. https://doi.org/10.3390/ph16101386
Cafaro V, Bosso A, Di Nardo I, D’Amato A, Izzo I, De Riccardis F, Siepi M, Culurciello R, D’Urzo N, Chiarot E, et al. The Antimicrobial, Antibiofilm and Anti-Inflammatory Activities of P13#1, a Cathelicidin-like Achiral Peptoid. Pharmaceuticals. 2023; 16(10):1386. https://doi.org/10.3390/ph16101386
Chicago/Turabian StyleCafaro, Valeria, Andrea Bosso, Ilaria Di Nardo, Assunta D’Amato, Irene Izzo, Francesco De Riccardis, Marialuisa Siepi, Rosanna Culurciello, Nunzia D’Urzo, Emiliano Chiarot, and et al. 2023. "The Antimicrobial, Antibiofilm and Anti-Inflammatory Activities of P13#1, a Cathelicidin-like Achiral Peptoid" Pharmaceuticals 16, no. 10: 1386. https://doi.org/10.3390/ph16101386