Bis-Indole Alkaloids Isolated from the Sponge Spongosorites calcicola Disrupt Cell Membranes of MRSA
Abstract
:1. Introduction
2. Results
2.1. MIC and MBC of the Bis-Indoles against Target Pathogens
2.2. Dose-Dependency and Time-Kill Kinetics
2.3. Bis-Indoles Induce Transient Small Colony Variants in MRSA
2.4. Mechanism of Action
2.5. Synergistic Effect of Bis-Indole Alkaloids with Aminoglycosides
2.6. Inhibition of Bacterial Cytotoxicity toward HeLa Cells
3. Discussion
4. Materials and Methods
4.1. Reagents and Bioactive Molecules
4.2. Bacterial and Mammalian Culture
4.3. Determination of MIC and MBC
4.4. Time-Kill Assay
4.5. Synergistic Effect of the Bis-Indoles in Combination with Traditional Antibiotics
4.6. Cytological Profiling and Fluorescence Microscopy
4.7. Inhibition of Bacterial Cytotoxicity toward HeLa Cells
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Gram-Positive Bacteria | Gram-Negative Bacteria | ||||||
---|---|---|---|---|---|---|---|
MRSA | MSSA | LM a | VP a | ST a | EC a | ||
Br-deoxy TP | MIC b | 25 | 25 | >50 | >50 | >50 | >50 |
MBC b | >50 | >50 | nd c | nd | nd | nd | |
Br-TP | MIC | 12.5 | 6.25 | 12.5 | 25 | >50 | >50 |
MBC | >50 | 25 | >50 | 25 | nd | nd | |
Spg-A | MIC | 12.5 | 12.5 | 25 | 25 | >50 | >50 |
MBC | 50 | 25 | 25 | 50 | nd | nd |
Bacteria | MICI a (mg L−1) | MICC b (mg L−1) | FICI c | |
---|---|---|---|---|
Antibiotic | Bis-Indole | Antibiotic + Bis-Indole | ||
MSSA | ||||
Gentamicin (0.25) | Br-deoxyTP (25) | Gentamicin + Br-deoxyTP (0.03 + 3.12) | 0.24 | |
Gentamicin (0.25) | Br-TP (6.25) | Gentamicin + Br-TP (0.06 + 1.56) | 0.48 | |
V. parahaemolyticus | ||||
Gentamicin (25) | Br-TP (25) | Gentamicin + Br-TP (6.25 + 1.5) | 0.31 | |
Gentamicin (25) | Spg-A (25) | Gentamicin + Spg-A (6.25 + 3.12) | 0.37 |
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Khan, N.A.; Kaur, N.; Owens, P.; Thomas, O.P.; Boyd, A. Bis-Indole Alkaloids Isolated from the Sponge Spongosorites calcicola Disrupt Cell Membranes of MRSA. Int. J. Mol. Sci. 2022, 23, 1991. https://doi.org/10.3390/ijms23041991
Khan NA, Kaur N, Owens P, Thomas OP, Boyd A. Bis-Indole Alkaloids Isolated from the Sponge Spongosorites calcicola Disrupt Cell Membranes of MRSA. International Journal of Molecular Sciences. 2022; 23(4):1991. https://doi.org/10.3390/ijms23041991
Chicago/Turabian StyleKhan, Neyaz A., Navdeep Kaur, Peter Owens, Olivier P. Thomas, and Aoife Boyd. 2022. "Bis-Indole Alkaloids Isolated from the Sponge Spongosorites calcicola Disrupt Cell Membranes of MRSA" International Journal of Molecular Sciences 23, no. 4: 1991. https://doi.org/10.3390/ijms23041991