Preclinical Evaluation of the Antimicrobial-Immunomodulatory Dual Action of Xenohormetic Molecules against Haemophilus influenzae Respiratory Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains, Media, Growth Conditions, and Drugs
2.2. Determination of Plant Extract and Pure Polyphenol Antimicrobial Effects
2.3. Determination of Antimicrobial Synergic Effects
2.4. Polyphenol Susceptibility Assays
2.5. Serial Passage Experiment with Polyphenol
2.6. Infection of Tissue Cultured Cells
2.7. RNA Extraction and Real-Time Quantitative PCR
2.8. Western Blotting
2.9. NTHi Mouse Lung Infection
2.10. NTHi Adult Zebrafish Infection
2.11. Statistical Analysis
3. Results
3.1. An Extract of Cistus salviifolius Rich in Polyphenols Has an Antimicrobial Effect on H. influenzae
3.2. Antimicrobial Effects of Quercetin, Myricetin, and Punicalagin against NTHi
3.3. Quercetin Modulates NTHi Infection of Cultured Airway Epithelial Cells
3.4. Quercetin Lowers Proinflammatory Gene Expression by Epithelial Cells Infected with H. influenzae
3.5. Antimicrobial and Anti-inflammatory Effects of Quercetin Administration on Mouse Lung Infection with NTHi
3.6. Quercetin Antimicrobial Protective Effect on Zebrafish Systemic Infection with NTHi
4. Discussion
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Combination (A + B) | MICA (µg/mL) | MICA (A + B Combination) | MICB (µg/mL) | MICB (A + B Combination) | ΣFIC | Result | |
---|---|---|---|---|---|---|---|
A | B | ||||||
Quercetin | Punicalagin | 167 | 83.5 | 320 | 160 | 1 | Indiferent |
Quercetin | Myricetin | 250 ± 118 | 167 | 800 | 125 ± 106 | 0.91 ± 0.22 | Indiferent |
Punicalagin | Myricetin | 320 | 80 | 800 | 800 | 1.25 | Indiferent |
Quercetin | Azm | 167 | 125.25 ± 59 | 1.5 ± 0.71 | 1.5 ± 0.71 | 2 ± 1.41 | Indiferent |
Myricetin | Azm | 400 | 12.5 | 1.5 ± 0.71 | 2 | 1.53 ± 0.71 | Indiferent |
Punicalagin | Azm | 320 | 50 ± 42.4 | 2 | 1.5 ± 0.71 | 0.91 ± 0.49 | Indiferent |
Quercetin | Amp | 125 ± 59 | 10.45 | 1 | 1.5 ± 0.71 | 1.6 ± 0.75 | Indiferent |
Myricetin | Amp | 400 | 800 | 1 | 2 | 4 | Indiferent |
Punicalagin | Amp | 320 | 640 | 1 | 0.13 | 2.13 | Indiferent |
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Fernández-Calvet, A.; Euba, B.; Caballero, L.; Díez-Martínez, R.; Menéndez, M.; Ortiz de Solórzano, C.; Leiva, J.; Micol, V.; Barrajón-Catalán, E.; Garmendia, J. Preclinical Evaluation of the Antimicrobial-Immunomodulatory Dual Action of Xenohormetic Molecules against Haemophilus influenzae Respiratory Infection. Biomolecules 2019, 9, 891. https://doi.org/10.3390/biom9120891
Fernández-Calvet A, Euba B, Caballero L, Díez-Martínez R, Menéndez M, Ortiz de Solórzano C, Leiva J, Micol V, Barrajón-Catalán E, Garmendia J. Preclinical Evaluation of the Antimicrobial-Immunomodulatory Dual Action of Xenohormetic Molecules against Haemophilus influenzae Respiratory Infection. Biomolecules. 2019; 9(12):891. https://doi.org/10.3390/biom9120891
Chicago/Turabian StyleFernández-Calvet, Ariadna, Begoña Euba, Lucía Caballero, Roberto Díez-Martínez, Margarita Menéndez, Carlos Ortiz de Solórzano, José Leiva, Vicente Micol, Enrique Barrajón-Catalán, and Junkal Garmendia. 2019. "Preclinical Evaluation of the Antimicrobial-Immunomodulatory Dual Action of Xenohormetic Molecules against Haemophilus influenzae Respiratory Infection" Biomolecules 9, no. 12: 891. https://doi.org/10.3390/biom9120891