New screens and targets in antibacterial drug discovery

As the supply of effective antibiotics dwindles and the emergence of multi-drug-resistant bacteria becomes more commonplace, there is an urgent need to identify novel antibacterial targets and leads with new mechanisms of action. Among the strategies to bolster our current scarcity of effective antibiotics are biochemical and phenotype-based screens, and the rational design of inhibitors. In this review we highlight some recent contributions that these methodologies have yielded, placing particular emphasis on screens capable of identifying novel leads involved in such processes as virulence; underexploited targets that reside in bacterial cell surfaces; the use of bacteriophage as antibiotic adjuvants; and novel targets of essential pathways. We discuss these findings in the context of the field of antibiotic drug discovery and how such discoveries position us to begin to fill the antibiotic gap that has been widening for the last half century.