New targets and strategies for the development of antibacterial agents.

The increasing incidence of bacterial drug-resistance is stimulating the development of strategies targeting previously unexploited mechanisms of antibiotic action. Combinatorial chemistry, which generates molecularly diverse compounds, target-directed strategies, and high-throughput screens are being used to detect potential antibacterial agents. Bacterial DNA replication and cell division are the targets of new screening methods, as are membrane proteins, particularly those constituting efflux pumps; two-component signalling systems are also being targeted. Secondary-screening methods are being developed to find antibiotics that destroy slowly growing or resting bacteria, and to evaluate whether new antibiotics will be active against intracellular bacteria.