Outlook for Genomic Technologies for Antibiotic Drug Discovery

The elucidation of sequence information for dozens to hundreds of microbial genomes represented the basis for the development of new genetic tests in various bacterial pathogens and the establishment of genomics technologies such as tran-scriptome and proteome analysis. Substantial technical progress in gene chip production, two-dimensional gel electrophoresis, and mass spectrometry greatly improved the reproducibility and throughput of transcriptome and proteome analysis. Equally importantly, software tools were elaborated and are constantly being improved to efficiently deal with the large data sets generated by genomics techniques. Although the first decade of genomics is over, the application of genomics techniques in antibiotic drug discovery is still in its early days. Time was needed to develop novel genetic tools and to generate reference compendia of genome-wide expression profiles which open up new avenues for target validation, whole-cell drug screening, and mode-of-action characterization of unexplored antimicrobials [75]. Some examples of successful application of genomics technologies, as described above, raise the hope that the contribution of genomics-based technologies to antibiotic drug discovery will significantly improve the success rate of antibiotic drug discovery in the near future. The genomics technologies in combination with the physiological knowledge about pathogens, which has been enormously increased in the genomics era, will make it possible to select from the pool of compounds with antibacterial activity those leads with a desired and promising biological profile more precisely than ever before. This will reduce the target-based attrition rates in later, more costly, stages of development.

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