Bacterial targets and antibiotics: genome-based drug discovery.
The requirement for novel classes of antibiotics to combat the emergence of resistant and multi-resistant bacteria has coincided with the completion sequencing of a number of bacterial genomes. The in silico analysis of these genomes coupled with innovative genetic manipulation has already led to the identification of conserved essential (either in vitro or in vivo, depending on the methodology) genes that are potential targets for antibacterial research. New technologies, made possible by access to the genomic sequences, are capable of simultaneously quantifying almost the entire complement of gene products synthesised by bacterial cells. These technologies are opening up the way for the analysis of expression patterns elicited in cells in response to changes in their environment. The integration of these technologies into the drug discovery process is still in its infancy and the potential wealth of information, some of it already available, has yet to be fully realised.
Gray
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CP
F. Hoffmann-La Roche Ltd, Pharma Research Preclinical, Infectious Diseases, Basel, Switzerland. christopher.gray@roche.com
Keck
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W
D000900:Anti-Bacterial Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005798:Genes, Bacterial / Q000235:genetics; D020043:Genes, Essential / Q000235:genetics; D016680:Genome, Bacterial; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome; D012984:Software; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
D000900:Anti-Bacterial Agents; D020543:Proteome