Target-Based Antimicrobial Drug Discovery - Bacterial Pathogenesis: Methods and Protocols - page 254

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Target-Based Antimicrobial Drug Discovery

Lefa E. Alksne and Paul M. Dunman

Summary
The continued increase in antibiotic resistance among bacterial pathogens, coupled with
a decrease in infectious disease research among pharmaceutical companies, has escalated
the need for novel and effective antibacterial chemotherapies. While current agents have
emerged almost exclusively from whole-cell screening of natural products and small
molecules that cause microbial death, recent advances in target identification and assay
development have resulted in a flood of target-driven drug discovery methods. Whether
genome-based methodologies will yield new classes of agents that conventional methods
have been unable to is yet to be seen. At the end of the day, perhaps a synergy between
old and new approaches will harvest the next generation of antibacterial treatments.

Key Words: Antibacterial; drug discovery; antibacterial target; antimicrobial

chemotherapy.

1. Introduction
In what is now sometimes referred to as the post-genomic age of microbi-
ology (1) , during which hundreds of sequenced bacterial genomes have been
mined for putatively essential genes, antibacterial drug discovery is primarily
target driven (2) . For better or worse, use of whole-cell assays in which the
only marker of antibacterial activity is growth inhibition or death are currently
rare. The multitude of gene products that have been identified as potential
antimicrobial targets, along with significant advancements in detection methods,
provide researchers with a new standard for attack (3) . The trick to successful
drug discovery, however, is to identify and pursue the right target with the right
method.