Novel genetic techniques and approaches in the microbial genomics era: identification and/or validation of targets for the discovery of new antibacterial agents.
The availability of microbial genome sequences has ushered in the genomics era and has led to numerous technical advancements over the past decade. These advances have been both in the bioinformatics field that has integrated computer-based approaches with biology and in research methods in the laboratory. The advances have assisted scientists in their study of bacterial gene complements and the roles of their gene products in the bacterial life cycle. Assignment of genes as essential to the bacterial cell nominated them as potential targets for antibacterial drugs and spurred attempts to exploit this information and convert it into drugs. At present, these efforts have met with minimal success. There are several possible reasons for these disappointing results including choice of targets and screen designs, compound libraries chosen for screens, and decreased commitment to antibacterial drug discovery by many large pharmaceutical companies. Structure-based approaches could become very effective in the future as methodologies continue to improve.
Pucci
Michael J
MJ
Achillion Pharmaceuticals Inc, New Haven, CT 06511, USA. mpucci@achillion.com
D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D004353:Drug Evaluation, Preclinical; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods*; D006801:Humans; D008962:Models, Theoretical; D013678:Technology, Pharmaceutical / Q000379:methods
D000900:Anti-Bacterial Agents