Discovery research: the scientific challenge of finding new antibiotics.

@article{Livermore2011DiscoveryRT,
  title={Discovery research: the scientific challenge of finding new antibiotics.},
  author={David M Livermore},
  journal={The Journal of antimicrobial chemotherapy},
  year={2011},
  volume={66 9},
  pages={
          1941-4
        }
}
  • D. Livermore
  • Published 1 September 2011
  • Biology
  • The Journal of antimicrobial chemotherapy
The dwindling supply of new antibiotics largely reflects regulatory and commercial challenges, but also a failure of discovery. In the 1990s the pharmaceutical industry abandoned its classical ways of seeking antibiotics and instead adopted a strategy that combined genomics with high-throughput screening of existing compound libraries. Too much emphasis was placed on identifying targets and molecules that bound to them, and too little emphasis was placed on the ability of these molecules to… 
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References

SHOWING 1-10 OF 31 REFERENCES
Why is big Pharma getting out of antibacterial drug discovery?
  • S. Projan
  • Political Science
    Current opinion in microbiology
  • 2003
Drugs for bad bugs: confronting the challenges of antibacterial discovery
TLDR
The experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years is shared, and what is learned is looked at and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.
Challenges of Antibacterial Discovery
  • L. Silver
  • Biology
    Clinical Microbiology Reviews
  • 2011
TLDR
The purpose of this review is to underscore and illustrate those scientific problems unique to the discovery and optimization of novel antibacterial agents that have adversely affected the output of the effort.
A guide to successful bioprospecting: informed by actinobacterial systematics
TLDR
The bioprospecting strategy is based upon the premise that new secondary metabolites can be found by screening relatively small numbers of dereplicated, novel actinomycetes isolated from marine sediments and is exemplified by the discovery of a range of novel bioactive compounds.
Type IIA topoisomerase inhibition by a new class of antibacterial agents
TLDR
This work provides new insights into the mechanism of topoisomerase action and a platform for structure-based drug design of a new class of antibacterial agents against a clinically proven, but conformationally flexible, enzyme class.
Discovery of a Novel and Potent Class of FabI-Directed Antibacterial Agents
TLDR
Results show that compound 4 is representative of a new, totally synthetic series of antibacterial agents that has the potential to provide novel alternatives for the treatment of S. aureus infections that are resistant to the present armory of antibiotics.
Mechanisms of RND multidrug efflux pumps.
Polymyxins and their novel derivatives.
  • M. Vaara
  • Biology, Chemistry
    Current opinion in microbiology
  • 2010
Medicinal plants and antimicrobial activity.
...
...