Small and lethal: searching for new antibacterial compounds with novel modes of action

The discovery of drugs used to combat infectious diseases is in the process of constant change to address the ever-worsening problem of antibiotic resistance in pathogens and a lack of recent success in discovering new antibacterial drugs. In the past 2 decades, research in both academia and industry has made use of molecular biology, genetics, and comparative genomics, which has led to the development of key technologies for the discovery of novel antibacterial agents. Genome-scale efforts have led to the identification of numerous molecular targets. Chemical diversity from synthetic combinatorial libraries and natural products is being used to screen for new molecules. A wide variety of approaches are being used in the search for novel antibiotics, and these can be categorized as being either biochemically focused or cell based. The over-riding goal of all methods in use today is to discover new chemical matter with novel mechanisms of action against drug-resistant pathogens.