Strategies to discover novel antimicrobials to cope with emerging medical needs

Abstract

The antibacterial screening strategies developed since the 1990s have seen an important evolution from the low throughput early phenotypic assays used to identify compounds targeting specific pathogens to target-based whole cell assays and structured-based design derived from in silico screening. Whereas empirical and target-based methods have been widely applied to screen for antibacterial agents, novel approaches such as structure-based drug design have proved to be a successful approach in other therapeutic areas, but they have not yet been widely applied to the development of antibacterial drugs. The objective of all these approaches has been the discovery of chemically novel leads that inhibit new molecular targets, or inhibit established targets by mechanisms distinct from those exploited by existing drugs. The focus of this chapter is to review a selection of different drug discovery paradigms that were developed to deliver novel antibacterial drugs as inhibitors of old and new essential bacterial targets proposed from single target to genome-wide initiatives. It also discusses some new trends in antibacterial discovery that have emerged with the rapid evolution and spread of antibiotic multi-resistances.