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Genomic approaches to antibacterial discovery
David J Payne1, Michael N Gwynn, David J Holmes
1Department of Microbiology, Microbial, Musculoskeletal, Proliferative Diseases Centr for Excellence and Drug Discovery, GlaxoSmithKline, Collegeville, PA, USA.
Methods in Molecular Biology (Clifton, N.J.)
|May 19, 2004
Summary
Genomics accelerates the discovery of new antibacterial agents through two main strategies: identifying novel drug targets and determining the mechanisms of action for existing compounds. This approach has yielded numerous potential treatments for infections.
Area of Science:
- Microbiology
- Genomics
- Drug Discovery
Background:
- The rise of antimicrobial resistance necessitates novel antibacterial agents.
- Genomics offers powerful tools for identifying new therapeutic targets and understanding drug mechanisms.
Purpose of the Study:
- To describe two primary strategies for discovering new antibacterial agents.
- To highlight the indispensable role of genomics in these discovery pipelines.
Main Methods:
- Genomic target-based screening using comparative genomics and bioinformatics to identify selective antibacterial targets.
- Activity-based screening followed by target identification using advanced biochemical and genomic technologies.
Main Results:
- Identification of an unprecedented number of novel antibacterial targets.
- Successful progression of a genomics-identified target from screening to preclinical efficacy.
- Characterization of the mode of action for compounds with existing antibacterial activity.
Conclusions:
- Genomics is crucial for both identifying novel antibacterial targets and elucidating the mechanisms of action of potential drug candidates.
- Both genomic target-based screening and activity-based screening are effective strategies for antibacterial discovery.