Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics
Abstract
:1. Introduction
2. Results
2.1. VanZ Modeling and Prediction of the VanZ Interaction with a Derivative of Benzimidazole
2.2. Molecular Dynamic Simulation of VanZ–G3K and Analysis
2.3. Synthesis and Characterization of G3K
2.4. In Vivo Validation of VanZ–G3K Interaction
3. Discussion
4. Materials and Methods
4.1. VanZ Protein Structure Prediction and Validation
4.2. Chemical Synthesis of G3K and Characterization
4.2.1. Chemicals
4.2.2. Synthesis
4.2.3. Nuclear Magnetic Resonance (NMR) Spectroscopy
4.2.4. High-Performance Liquid Chromatography (HPLC)
4.3. Protein Pocket Analysis and Molecular Docking
4.4. Molecular Dynamic Simulation (MDS) Analysis
4.5. In Vivo Investigation
4.5.1. Bacterial Strains
4.5.2. Activity of G3K In Vivo against VanZ Expressing Bacterial Strains
G3K’s Effect against Gram-Positive Bacteria
The Effect of G3K in Combination with TEI on VanZ-Mediated Teicoplanin Resistance in S. aureus
G3K in Combination with TEI against S. pneumonia Strains and Clinical Variants of E. faecium and Susceptibility Testing
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
References
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Sur, V.P.; Mazumdar, A.; Vimberg, V.; Stefani, T.; Androvic, L.; Kracikova, L.; Laga, R.; Kamenik, Z.; Komrskova, K. Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics. Int. J. Mol. Sci. 2022, 23, 97. https://doi.org/10.3390/ijms23010097
Sur VP, Mazumdar A, Vimberg V, Stefani T, Androvic L, Kracikova L, Laga R, Kamenik Z, Komrskova K. Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics. International Journal of Molecular Sciences. 2022; 23(1):97. https://doi.org/10.3390/ijms23010097
Chicago/Turabian StyleSur, Vishma Pratap, Aninda Mazumdar, Vladimir Vimberg, Tommaso Stefani, Ladislav Androvic, Lucie Kracikova, Richard Laga, Zdenek Kamenik, and Katerina Komrskova. 2022. "Specific Inhibition of VanZ-Mediated Resistance to Lipoglycopeptide Antibiotics" International Journal of Molecular Sciences 23, no. 1: 97. https://doi.org/10.3390/ijms23010097