Genomics-based identification of targets in pathogenic bacteria for potential therapeutic and diagnostic use.
The availability of numerous complete microbial genome sequences has profoundly altered our understanding of a number of fundamental biological processes. For example the enzymes involved in aminoacyl-tRNA (AA-tRNA) synthesis, the key process responsible for the accuracy of protein synthesis, have been found to be highly species-specific. In particular, a number of pathogens contain certain pathways of AA-tRNA synthesis that are unrelated to those 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 recent advances in the elucidation of AA-tRNA synthesis pathways and discuss the possible pharmaceutical exploitation of these discoveries. In particular, the integration of genomic and biochemical approaches to identify novel targets for the treatment of Chlamydial infections and the diagnosis and treatment of Lyme disease will be presented.
Department of Molecular Biophysics and Biochemistry, Yale University, PO Box 208114, 266 Whitney Avenue, New Haven, CT 06520-8114, USA.
G
G
Raczniak
M
M
Ibba
D
D
Söll
D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D015748:Borrelia burgdorferi Group / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D002690:Chlamydia Infections / Q000188:drug therapy; D002692:Chlamydia trachomatis / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D016680:Genome, Bacterial; D008193:Lyme Disease / Q000175:diagnosis / Q000188:drug therapy; D020543:Proteome / Q000096:biosynthesis / Q000187:drug effects; D012343:RNA, Transfer / Q000096:biosynthesis
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D020543:Proteome; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases