Synergy between Ursolic and Oleanolic Acids from Vitellaria paradoxa Leaf Extract and β-Lactams against Methicillin-Resistant Staphylococcus aureus: In Vitro and In Vivo Activity and Underlying Mechanisms
Abstract
:1. Introduction
2. Results and Discussion
2.1. Analysis and Quantification of Major Components of the Vitellaria paradoxa Crude Extract
2.2. Antimicrobial Activity of the Crude Extract’s Major Components
2.3. Effect of OA and UA on PBP2 Recruitment to the Septum
2.4. Evaluation of β-Lactamase Activity
2.5. Murine Model of Subcutaneous Infection
3. Materials and Methods
3.1. Plant Material
3.2. Preparation of Extracts
3.3. Reference Compounds
3.4. UA and OA Identification
3.5. UA and OA Quantification
3.6. Bacteria Strains
3.7. Minimal Inhibitory Concentration (MIC) Determination
3.8. Fractional Inhibitory Concentration Indices (FICI) Determination
3.9. Time-Kill Assay
3.10. Effect of Compounds on PBP2 Localization
3.11. Effect of Compounds on PBP2 and PBP2A Expression
3.12. Evaluation of β-Lactamase Activity using the Nitrocefin Test
3.13. Murine Model of Subcutaneous Infection
3.14. Statistical Analysis
Supplementary Materials
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are available from the authors. |
Strain | MIC (mg/L) | FICI | ||||||
---|---|---|---|---|---|---|---|---|
UA | OA | Ampicillin | Oxacillin | Ampicillin-UA | Ampicillin-OA | Oxacillin-UA | Oxacillin-OA | |
ATCC 33591 | 16 | 32 | 64 | 32 | 0.38–1 | 0.31–1 | 0.25–1 | 0.16–1 |
VUB 2 | 8 | 64 | 32 | 64 | 0.50–1 | 0.25–1 | 0.31–1 | 0.18–1 |
VUB 10 | 8 | 64 | 128 | 128 | 0.37–1 | 0.31–1 | 0.31–1 | 0.18–1 |
VUB 20 | 8 | 64 | 64 | 256 | 0.37–1 | 0.25–1 | 0.50–1 | 0.37–1 |
VUB 30 | 16 | 128 | 32 | 512 | 0.56–1 | 0.37–1 | 0.50–1 | 0.25–1 |
Compound | MIC (mg/L) | FICI | |
---|---|---|---|
OXA | NAF | ||
UA | 64 | 0.31–1 | 0.28–1 |
OA | >128 | 0.50–1 | 0.56–1 |
OXA | 32 | - | - |
NAF | 32 | - | - |
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Catteau, L.; Reichmann, N.T.; Olson, J.; Pinho, M.G.; Nizet, V.; Van Bambeke, F.; Quetin-Leclercq, J. Synergy between Ursolic and Oleanolic Acids from Vitellaria paradoxa Leaf Extract and β-Lactams against Methicillin-Resistant Staphylococcus aureus: In Vitro and In Vivo Activity and Underlying Mechanisms. Molecules 2017, 22, 2245. https://doi.org/10.3390/molecules22122245
Catteau L, Reichmann NT, Olson J, Pinho MG, Nizet V, Van Bambeke F, Quetin-Leclercq J. Synergy between Ursolic and Oleanolic Acids from Vitellaria paradoxa Leaf Extract and β-Lactams against Methicillin-Resistant Staphylococcus aureus: In Vitro and In Vivo Activity and Underlying Mechanisms. Molecules. 2017; 22(12):2245. https://doi.org/10.3390/molecules22122245
Chicago/Turabian StyleCatteau, Lucy, Nathalie T. Reichmann, Joshua Olson, Mariana G. Pinho, Victor Nizet, Françoise Van Bambeke, and Joëlle Quetin-Leclercq. 2017. "Synergy between Ursolic and Oleanolic Acids from Vitellaria paradoxa Leaf Extract and β-Lactams against Methicillin-Resistant Staphylococcus aureus: In Vitro and In Vivo Activity and Underlying Mechanisms" Molecules 22, no. 12: 2245. https://doi.org/10.3390/molecules22122245