Antibiotic Discovery: Where Have We Come from, Where Do We Go?

Area of Science:

• Microbiology
• Pharmacology
• Drug Discovery

Background:

• Increasing antibiotic resistance and a low rate of new antibiotic approvals threaten effective treatment of infectious diseases.
• Historical antibiotic discovery relied on systematic platforms (Waksman, semi-synthesis, synthetic) yielding major antibiotic classes.
• The genomics era's target-based drug discovery proved limited, leading to a resurgence in cell-based platforms.

Purpose of the Study:

• To review historical and current antibiotic discovery platforms.
• To highlight the limitations of past approaches and the importance of cell-based methods.
• To emphasize the potential of microbial metabolism data in the post-genomic era for discovering new therapeutics.

Main Methods:

• Review of historical antibiotic discovery methodologies and platforms.
• Analysis of the successes and failures of different drug discovery eras (genomics vs. post-genomic).
• Discussion of the role of microbial metabolism in contemporary drug development.

Main Results:

• Major antibiotic classes were discovered through systematic, platform-driven approaches.
• Target-based drug discovery in the genomics era faced significant translational challenges.
• Cell-based platforms remain critical, and post-genomic data offers new avenues.

Conclusions:

• The pipeline for new antibiotics, especially with novel mechanisms, remains insufficient.
• Harnessing microbial metabolism data is crucial for developing next-generation antibiotics.
• Innovative platforms are essential to regain the upper hand in the fight against infectious diseases.