Genomics-based identification of targets in pathogenic bacteria for potential therapeutic and diagnostic use

The availability of numerous complete microbial genome sequences has profou ndly altered our understanding of a number of fundamental biological proces ses. For example the enzymes involved in aminoacyl-tRNA (AA-tRNA) synthesis , the key process responsible for the accuracy of protein synthesis, have b een found to be highly species-specific. In particular, a number of pathoge ns contain certain pathways of AA-tRNA synthesis that are unrelated to thos e found in their mammalian hosts. Since AA-tRNA synthesis is indispensable for cell viability, the discovery of pathogen-specific pathways and enzymes presents novel therapeutic and diagnostic targets. Here we will review rec ent advances in the elucidation of AA-tRNA synthesis pathways and discuss t he possible pharmaceutical exploitation of these discoveries. In particular , the integration of genomic and biochemical approaches to identify novel t argets for the treatment of Chlamydial infections and the diagnosis and tre atment of Lyme disease will be presented. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.