Genomics and the Prospects for the Discovery of New Targets for Antibacterial and Antifungal Agents

The current increase in the number of microbes resistant to antibacterial or antifungal agents represents a potential crisis in human and veterinary medicine. Some believe that we are entering a postantibiotic era where most antibiotics no longer will be efficacious. Therefore, it is important that new antibiotics be developed. However, because of the potential for cross-resistance, new targets for the discovery of antibiotics are needed particularly where resistance does not currently exist. The results obtained from the sequencing of genomes from pathogenic bacterial and fungal microbes provide an opportunity to ameliorate this problem. Genomic sequence data can be used to identify new genes that could be used as targets for new antibiotic discoveries. Viable new target genes might represent those that are widely distributed among pathogens or that have homologs and are essential for the viability of the organism. Chemical compounds that attack such targets would be expected to have classical antibiotic activities. Less widely distributed genes still could be valuable targets for narrow spectrum antibiotics. While many of these genes will have known or putative functions based on DNA sequence homology, the most interesting genes are the newly discovered genes with unknown functions. In this paper, it is suggested that novel, non-traditional targets also will be found through the analysis of genome sequences: those that are involved in disease pathogenesis and those that are involved in adaptation and growth in infection sites. The advantage of the non-classical targets is that targeting these sites may not result in the same degree of selective pressure that encourages resistance, and these could have a longer therapeutic life time.