Drug resistance in bacteria: history, genetics and biochemistry.

The significance of the discovery of prontosil in 1932 as the initiating step in the development of the modern era of antimicrobial chemotherapy is reviewed. The history of the discovery and the development of chemotherapeutic agents, from penicillin in 1929 to present-day antibiotics, are summarized. The various mechanisms by which bacteria are able to overcome the protective effects of these therapeutic agents (from the sulphonamides to the new fluoroquinolones) and develop resistance to them are discussed in detail. Attempts to elucidate the mechanisms by which resistance to chemotherapeutic agents develops are vital to the future of antimicrobial chemotherapy.