Genome to antibiotic targets
As discussed in last blog, genome sequencing has revolutionized several fields in biology, antibiotic target discovery being one of them. Antibiotic targets can be of 2 types:
1) Proteins those are essential for bacterial growth.
2) Proteins those are required for virulence.
Such proteins can be identified by mutating all the genes from a pathogen, one at a time, and observing for the desired phenotype. STM is still another approach (discussed in previous blog). All these approaches, however, are labour intensive.
The simplest alternative is provided by comparative genomic analysis of a pathogen with closely related non-pathogenic organisms. Genes of the pathogenic bacteria, which are absent from other bacteria, are likely to be responsible for its virulence and can be reliably selected for further screening. If genes essential for growth have to be targeted, then comparison is performed with smaller genomes, such as those of mycoplasmas, which contain only growth-essential genes. Every gene from this set can potentially be targeted for antibacterial development.
The genes short-listed by above approaches are then knocked out one-by-one for testing their essentiality in pathogenesis. Once the target genes have been selected, high throughput assay systems are developed to screen chemicals that can inhibit specific biochemical reactions catalyzed by these gene products.
