Dysregulation of Mycobacterium marinum ESX-5 Secretion by Novel 1,2,4-oxadiazoles
Abstract
:1. Introduction
2. Materials and Methods
2.1. Bacterial Strains, Cell Lines, and Culture Conditions
2.2. Reagents and Chemical Synthesis
2.3. Bacterial Susceptibility Assay and Cytotoxicity Testing
2.4. Lipase Activity Assay
2.5. Protein Secretion Analysis
2.6. Mtb Macrophage Infection Experiments
2.7. Proteomic Analysis
2.8. Construction of the Reporter Plasmid and Reporter Assay
2.9. Zebrafish Embryos Infection Experiments and Data Analysis
3. Results
3.1. Characterization of 1,2,4-oxadiazole Derivatives Using ESX-5 Secretion Reporter Assay
3.2. The 1,2,4-oxadiazole Derivatives 36.1 and 36.3 Elicit Hypersecretion of ESX-5 PE_PGRS Substrates
3.3. The 1,2,4-oxadiazole Derivatives 36.1 and 36.3 Induced the Overexpression of PE_PGRS MMAR_5294
3.4. 1,2,4-oxadiazoles Display Significant in vivo Activity
4. Discussion
Supplementary Materials
Author Contributions
Funding
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Protein | Average Count DMSO-Treated | Average Count 36.3-Treated | Fold Change | p-Value |
---|---|---|---|---|
MMAR_3268 MMAR_3271 MMAR_3279 MMAR_0851 | 0 | 38.39 | ∞ | 0.0004 |
MMAR_5294 | 0 | 13.77 | ∞ | 0.0032 |
CobN | 0 | 7.98 | ∞ | 0.0082 |
MMAR_4621 | 0 | 9.605 | ∞ | 0.0055 |
MmpL5 | 1.11 | 28.29 | 25.40 | 0.001 |
MMAR_5283 | 1.11 | 9.42 | 8.46 | 0.0322 |
DnaE1 | 6.68 | 33.62 | 5.03 | 0.0125 |
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Ho, V.Q.T.; Rong, M.K.; Habjan, E.; Bommer, S.D.; Pham, T.V.; Piersma, S.R.; Bitter, W.; Ruijter, E.; Speer, A. Dysregulation of Mycobacterium marinum ESX-5 Secretion by Novel 1,2,4-oxadiazoles. Biomolecules 2023, 13, 211. https://doi.org/10.3390/biom13020211
Ho VQT, Rong MK, Habjan E, Bommer SD, Pham TV, Piersma SR, Bitter W, Ruijter E, Speer A. Dysregulation of Mycobacterium marinum ESX-5 Secretion by Novel 1,2,4-oxadiazoles. Biomolecules. 2023; 13(2):211. https://doi.org/10.3390/biom13020211
Chicago/Turabian StyleHo, Vien Q. T., Mark K. Rong, Eva Habjan, Samantha D. Bommer, Thang V. Pham, Sander R. Piersma, Wilbert Bitter, Eelco Ruijter, and Alexander Speer. 2023. "Dysregulation of Mycobacterium marinum ESX-5 Secretion by Novel 1,2,4-oxadiazoles" Biomolecules 13, no. 2: 211. https://doi.org/10.3390/biom13020211