Potential Tamoxifen Repurposing to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli
Abstract
:1. Introduction
2. Results
2.1. Bone Marrow Immune Cells Migrate in Response to Monocyte Chemotactic Protein-1 (MCP-1) and Interleukin-18 (IL-18) during Bacterial Infection
2.2. Tamoxifen Impairs the Migration of Immune Cells from Bone Marrow to Blood
2.3. Tamoxifen Enhances Bacterial Killing by Macrophages and Neutrophils In Vitro
2.4. Tamoxifen Increases Mice Survival and Decreases the Bacterial Burden in a Murine Sepsis Model of A. Baumannii, P. Aeruginosa, and E. Coli
2.5. Direct Treatment with Tamoxifen Increases Mice Survival and Decreases the Bacterial Burden in a Murine Sepsis Model of A. Baumannii
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Bacterial Strains
4.3. Animals
4.4. A. Baumannii, P. Aeruginosa, and E. Coli Peritoneal Sepsis Models
4.5. Therapeutic Effect of Tamoxifen in Immunocompetent Murine Models of Peritoneal Sepsis
4.6. Flow Cytometry
4.7. Cytokine Assays
4.8. Cell Culture and Infection
4.9. Western Blot Immunoblotting
4.10. Macrophages Adhesion Assay
4.11. Neutrophil Killing Assay
4.12. Statistical Analysis
5. 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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Strain | Treatment | N | Bacterial Load (log CFU/g or mL ± SEM) | 3-Days Survival (%) | ||
---|---|---|---|---|---|---|
Spleen | Lung | Blood | ||||
A. baumannii ATCC 17978 | CTL | 6 | 9.51 ± 0.17 | 9.77 ± 0.17 | 6.14 ± 0.94 | 0 |
TAM | 6 | 2.87 ± 1.21 a | 2.61 ± 1.07 a | 0.61 ± 0.61 a | 100 a | |
P. aeruginosa PAO1 | CTL | 5 | 8.91 ± 0.15 | 9.24 ± 0.17 | 6.71 ± 0.27 | 0 |
TAM | 6 | 5.33 ± 1.08 b | 4.14 ± 1.50 b | 1.26 ± 1.26 b | 66.7 b | |
E. coli ATCC 25922 | CTL | 6 | 8.71 ± 0.05 | 8.88 ± 0.16 | 8.18 ± 0.37 | 0 |
TAM | 6 | 5.01 ± 1.20 c | 4.72 ± 1.08 c | 3.87 ± 0.99 c | 83.3c |
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Miró-Canturri, A.; Ayerbe-Algaba, R.; del Toro, R.; Mejías, M.E.-J.; Pachón, J.; Smani, Y. Potential Tamoxifen Repurposing to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli. Pharmaceuticals 2021, 14, 507. https://doi.org/10.3390/ph14060507
Miró-Canturri A, Ayerbe-Algaba R, del Toro R, Mejías ME-J, Pachón J, Smani Y. Potential Tamoxifen Repurposing to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli. Pharmaceuticals. 2021; 14(6):507. https://doi.org/10.3390/ph14060507
Chicago/Turabian StyleMiró-Canturri, Andrea, Rafael Ayerbe-Algaba, Raquel del Toro, Manuel Enrique-Jiménez Mejías, Jerónimo Pachón, and Younes Smani. 2021. "Potential Tamoxifen Repurposing to Combat Infections by Multidrug-Resistant Gram-Negative Bacilli" Pharmaceuticals 14, no. 6: 507. https://doi.org/10.3390/ph14060507