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JAC Advance Access originally published online on March 13, 2003
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Journal of Antimicrobial Chemotherapy (2003) 51, 749-752
© 2003 The British Society for Antimicrobial Chemotherapy

Leading Article

The role of genomics in antimicrobial discovery

Scott D. Mills*

AstraZeneca R&D Boston, Infection Discovery, 35 Gatehouse Drive, Waltham, MA 02451, USA

Keywords: genomics, antimicrobial, antibiotic, target-based

The first 150 words of the full text of this article appear below.


   Introduction
 
The majority of today’s most effective classes of antimicrobials originated many decades ago as natural products isolated from soil-colonizing bacteria and fungi. Several of these antibiotics were amenable to semi-synthetic chemistry, and as a result the antimicrobial industry has excelled at fine-tuning these existing classes of antibiotics to improve their spectrum, efficacy and safety. Conversely, there are very few examples of novel synthetic antimicrobials. Linezolid, an oxazolidinone antimicrobial,1 represents the first significant synthetic compound class introduced to the market in >25 years, since compounds of the quinolone class were optimized into today’s very successful fluoroquinolones.2

In 1969, US Surgeon General William Stewart testified before US Congress that it was time to ‘...close the book on infectious diseases...’. In addition, during the 1980s, antimicrobial research and development had limited appeal to the pharmaceutical industry due to the large number of effective products on the market and increasing generic substitution.3 In contrast . . . [Full Text of this Article]


   Microbial genomics
 

   Genomics and target-based antimicrobial discovery
 

   Peptide deformylase
 

   Methionyl tRNA synthetase
 

   Target-based whole-cell screening assays
 

   LpxC
 

   DNA microarrays
 

   Conclusions
 

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