New Targets for Antibacterial Compounds
Lynn L. Silver
from: Antibiotics: Current Innovations and Future Trends (Edited by: Sergio Sánchez and Arnold L. Demain). Caister Academic Press, U.K. (2015) Pages: 249-274.
Resistance to antibacterials underwent a noticeable rise starting in the mid-1980's, at a time when natural product screening for antibacterial antibiotics had become less productive. The advent of genome sequencing of bacteria, starting in 1995 seemed to provide an answer to the resistance problem: find new gene products to target in order to find antibacterial agents that were different from previous classes and unlikely to be cross-resistant with them. This plan relied on the assumption that the limitation to discovery was a lack of novel targets. As the search for antibacterials over the past twenty years has been largely directed toward finding inhibitors of novel targets, and that search has been largely unproductive, it seems likely that the assumption that targets are rate limiting is wrong. This chapter will discuss the characteristics that define good targets, with an emphasis on recognizing the potential for rapid resistance development with single-gene targets. Until it is robustly demonstrated that combinations of single-targeted agents can prevent or retard resistance development (as is seen with tuberculosis, HIV and HCV) and a regulatory pathway is established to develop such combinations, it may be that we will have to depend on the successful targets that have already been found and exploited read more ...