Combination of Amphiphilic Cyclic Peptide [R4W4] and Levofloxacin against Multidrug-Resistant Bacteria
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis and Purification of the Compounds
2.2. Antibacterial Activity
2.3. Combination Studies Using Levo and Peptides
2.4. Hemolytic Study
2.5. Cytotoxicity Assay
2.6. Time Kill Kinetics
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Design and Synthesis of Levo-[W4R3K] Conjugate
3.3. Antibacterial Activity
3.3.1. Bacterial Strains
3.3.2. Determination of Minimal Inhibitory Concentrations (MICs)
3.3.3. Checkerboard Assay
3.4. Hemolysis Assay
3.5. Cytotoxicity Assay
3.6. Time-Kill Kinetics Assay
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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Bacterial Strain | MIC (µg/mL) (µM) a | ||||||
---|---|---|---|---|---|---|---|
Levo | (R4W4) | [R4W4] | (Levo-C10-KR3W4) | [Levo-C10-KR3W4] | Levo + (R4W4) b | Levo + [R4W4] b | |
S. aureus (ATCC 29213) | 3.13 | 6.25 | 3.13 | 12.5 | 25 | 3.13 | 3.13 |
(8.66) | (4.51) | (2.28) | (6.67) | (13.45) | |||
S. aureus (ATCC BAA-1556) c | 3.13 | 6.25 | 3.13 | 12.5 | 50 | 3.13 | 6.25 |
(8.66) | (4.51) | (2.28) | (6.67) | (26.90) | |||
E. coli (ATCC 25922) | 50 | 25 | 6.25 | 50 | 50 | 12.5 | 12.5 |
(138.36) | (18.03) | (4.55) | (26.68) | (26.90) | |||
E. coli (ATCC BAA-2452) d,e | 50 | 50 | 12.5 | 50 | 100 | 25 | 12.5 |
(138.36) | (36.06) | (9.11) | (26.68) | (53.79) | |||
P. aeruginosa (ATCC 27883) | 0.78 | 25 | 12.5 | 100 | 100 | 1.56 | 1.56 |
(2.16) | (18.03) | (9.11) | (53.36) | (53.79) | |||
P. aeruginosa (ATCC BAA-1744) e | 0.78 | 25 | 12.5 | 100 | >100 | 1.56 | 0.78 |
(2.16) | (18.03) | (9.11) | (53.36) | (>53.79) | |||
K. pneumoniae (ATCC 13883) | 25 | 50 | 12.5 | 25 | 50 | 25 | 12.5 |
(69.18) | (36.06) | (9.11) | (13.34) | (26.90) | |||
K. pneumoniae (ATCC BAA-1705) f | 50 | 25 | 12.5 | 50 | 50 | 12.5 | 12.5 |
(138.36) | (18.03) | (9.11) | (26.68) | (26.90) |
Bacterial Strain | MIC in Combination (µg/mL) | FICI a | ||||
---|---|---|---|---|---|---|
Levo/(R4W4) | Levo/[R4W4] | Levo + (R4W4) | Interactive Category | Levo + [R4W4] | Interactive Category | |
S. aureus (ATCC 29213) | 1.56/1.56 | 0.78/1.56 | 0.748 | Partial synergy | 0.748 | Partial synergy |
S. aureus (ATCC BAA-1556) | 1.56/3.13 | 0.78/0.78 | 0.999 | Partial synergy | 0.498 | Synergy |
E. coli (ATCC 25922) | 25/12.5 | 6.25/1.56 | 1 | Indifference | 0.374 | Synergy |
E. coli (ATCC BAA-2452) | 25/12.5 | 3.13/3.13 | 0.75 | Partial synergy | 0.313 | Synergy |
P. aeruginosa (ATCC 27883) | 0.78/1.56 | 0.15/1.56 | 1.062 | Indifference | 0.317 | Synergy |
P. aeruginosa (ATCC BAA-1744) | 0.39/1.56 | 0.07/1.56 | 0.562 | Partial Synergy | 0.214 | Synergy |
K. pneumoniae (ATCC 13883) | 25/12.5 | 6.25/3.13 | 1.25 | Indifference | 0.500 | Synergy |
K. pneumoniae (ATCC BAA-1705) | 25/12.5 | 12.5/1.56 | 1 | Indifference | 0.374 | Synergy |
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Sajid, M.I.; Lohan, S.; Kato, S.; Tiwari, R.K. Combination of Amphiphilic Cyclic Peptide [R4W4] and Levofloxacin against Multidrug-Resistant Bacteria. Antibiotics 2022, 11, 416. https://doi.org/10.3390/antibiotics11030416
Sajid MI, Lohan S, Kato S, Tiwari RK. Combination of Amphiphilic Cyclic Peptide [R4W4] and Levofloxacin against Multidrug-Resistant Bacteria. Antibiotics. 2022; 11(3):416. https://doi.org/10.3390/antibiotics11030416
Chicago/Turabian StyleSajid, Muhammad Imran, Sandeep Lohan, Shun Kato, and Rakesh Kumar Tiwari. 2022. "Combination of Amphiphilic Cyclic Peptide [R4W4] and Levofloxacin against Multidrug-Resistant Bacteria" Antibiotics 11, no. 3: 416. https://doi.org/10.3390/antibiotics11030416