Antibacterial drug discovery--then, now and the genomics future

Abstract

Drug discovery research in the area of infectious diseases, in particular that dealing with antibacterial/antibiotic susceptibility and resistance, is in a process of continuing evolution. Steeped in the history of the highly successful intervention with chemotherapeutic agents to treat human infections, the emergence of drug-resistant pathogens worldwide presents a serious unmet medical need, if not a pending catastrophe. Research in both academia and industry over the past 30 years using molecular biology, genetics and more recently--bacterial genomics--has assembled key enabling technologies to increase productivity and success rates in the discovery and development of novel antibacterial agents. However genomics is not limited only to antibacterial target selection but provides the opportunity to further understand key interactions in the use of antibacterial compounds as therapeutic agents (such as resistance emergence, susceptibility, efflux, interactions between compound and pathogen, etc.). Genomics also offers the potential for insights into: bacterial niche adaptation, host susceptibility, treatment regimens, antibiotic resistance, pharmacokinetics (e.g., host metabolism differences), safety and the microbial genesis of chronic diseases (e.g., gastric ulceration).