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Generating Transposon Insertion Libraries in Gram-Negative Bacteria for High-Throughput Sequencing
Published on: July 7, 2020
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Polymyxins: a new hope in combating Gram-negative superbugs?
Tony Velkov1, Kade D Roberts1, Philip E Thompson2
1Drug Delivery, Disposition & Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville 3052, Victoria, Australia.
Future Medicinal Chemistry
|June 22, 2016
Summary
New polymyxin antibiotics are needed to fight Gram-negative superbugs, but current drugs cause kidney damage. Despite extensive research, no safer polymyxins have reached patients yet.
Area of Science:
- Medicinal chemistry
- Antimicrobial drug discovery
- Pharmacology
Background:
- Polymyxins are crucial last-resort antibiotics against multidrug-resistant Gram-negative bacteria.
- Nephrotoxicity of existing polymyxins (polymyxin B, colistin) limits their clinical application.
- Significant efforts have been made globally to develop safer and more effective polymyxin analogs.
Purpose of the Study:
- To provide an overview of current polymyxin drug discovery programs.
- To analyze the progress from a medicinal chemistry standpoint.
- To offer insights for future successful polymyxin development.
Main Methods:
- Review of ongoing and past polymyxin drug discovery initiatives.
- Medicinal chemistry analysis of structural modifications and their impact.
- Evaluation of efficacy and safety profiles of novel polymyxin candidates.
Main Results:
- Despite a decade of research, no new polymyxin drugs have been approved for clinical use.
- Various academic and industrial programs are exploring different chemical strategies.
- Challenges remain in balancing antibacterial activity with reduced toxicity.
Conclusions:
- The development of safer polymyxins is critical for combating resistant Gram-negative infections.
- Medicinal chemistry plays a pivotal role in overcoming the nephrotoxicity of polymyxins.
- Future strategies must focus on innovative approaches to achieve clinical success.
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