Different drugs for bad bugs: antivirulence strategies in the age of antibiotic resistance

Efforts to combat bacterial infections by targeting virulence factors are gaining traction, fuelled by the potential to circumvent the development of antibacterial resistance and recent landmark approvals of antivirulence drugs. Here, Otto and colleagues examine the antivirulence drugs in development, highlighting the most promising targets and strategies, as well as caveats to using this approach. The rapid evolution and dissemination of antibiotic resistance among bacterial pathogens are outpacing the development of new antibiotics, but antivirulence agents provide an alternative. These agents can circumvent antibiotic resistance by disarming pathogens of virulence factors that facilitate human disease while leaving bacterial growth pathways — the target of traditional antibiotics — intact. Either as stand-alone medications or together with antibiotics, these drugs are intended to treat bacterial infections in a largely pathogen-specific manner. Notably, development of antivirulence drugs requires an in-depth understanding of the roles that diverse virulence factors have in disease processes. In this Review, we outline the theory behind antivirulence strategies and provide examples of bacterial features that can be targeted by antivirulence approaches. Furthermore, we discuss the recent successes and failures of this paradigm, and new developments that are in the pipeline.