Dual GSK-3β/HDAC Inhibitors Enhance the Efficacy of Macrophages to Control Mycobacterium tuberculosis Infection
Abstract
:1. Introduction
2. Materials and Methods
2.1. Differentiation of Human Monocyte-Derived Macrophages (hMDMs)
2.2. Preparation of Mycobacterial Cultures
2.3. Mycobacterial Infection of hMDMs
2.4. Flow Cytometry
2.5. Test and Control Compounds
2.6. High-Content Imaging with IncuCyte
2.7. Colony Forming Unit (CFU) Counts
2.8. TaqMan Array Cards for Quantitative PCR
2.9. Statistics
3. Results
3.1. Phenotypic Screening of Dual GSK-3β and HDAC1/HDAC6 Inhibitor Candidates Using a Human Macrophage Infection Model
3.2. Evaluating the Efficacy of Dual GSK-3β and HDAC1/HDAC6 Inhibitor Candidates in Reducing the Growth of Avirulent H37Ra in Human Macrophages
3.3. Evaluating the Efficacy of Dual GSK-3β and HDAC1/HDAC6 Inhibitor Candidates in Reducing the Growth of Virulent H37Rv in Human Macrophages
3.4. Modulation of Mtb-Infected Macrophage Responses upon Treatment with the GSK-3β Inhibitor SB415286 and Compounds C02 and C06
4. Discussion
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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Kalsum, S.; Xu, R.; Akber, M.; Huang, S.; Lerm, M.; Chen, Y.; Lourda, M.; Zhou, Y.; Brighenti, S. Dual GSK-3β/HDAC Inhibitors Enhance the Efficacy of Macrophages to Control Mycobacterium tuberculosis Infection. Biomolecules 2025, 15, 550. https://doi.org/10.3390/biom15040550
Kalsum S, Xu R, Akber M, Huang S, Lerm M, Chen Y, Lourda M, Zhou Y, Brighenti S. Dual GSK-3β/HDAC Inhibitors Enhance the Efficacy of Macrophages to Control Mycobacterium tuberculosis Infection. Biomolecules. 2025; 15(4):550. https://doi.org/10.3390/biom15040550
Chicago/Turabian StyleKalsum, Sadaf, Ruilan Xu, Mira Akber, Shengjie Huang, Maria Lerm, Yuqing Chen, Magda Lourda, Yang Zhou, and Susanna Brighenti. 2025. "Dual GSK-3β/HDAC Inhibitors Enhance the Efficacy of Macrophages to Control Mycobacterium tuberculosis Infection" Biomolecules 15, no. 4: 550. https://doi.org/10.3390/biom15040550
APA StyleKalsum, S., Xu, R., Akber, M., Huang, S., Lerm, M., Chen, Y., Lourda, M., Zhou, Y., & Brighenti, S. (2025). Dual GSK-3β/HDAC Inhibitors Enhance the Efficacy of Macrophages to Control Mycobacterium tuberculosis Infection. Biomolecules, 15(4), 550. https://doi.org/10.3390/biom15040550