Antibiotics for Emerging Pathogens

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Science  28 Aug 2009:
Vol. 325, Issue 5944, pp. 1089-1093
DOI: 10.1126/science.1176667

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  1. Fig. 1

    Multidrug-resistant strains of these bacterial pathogens are on the rise. [Credit: Dennis Kunkel Microscopy, Incorporated]

  2. Fig. 2

    Synthetic tailoring is widely used to create successive generations of antibiotic classes. Scaffolds are colored black; peripheral chemical modifications are colored red. The quinolone scaffold is synthetic, whereas the other scaffolds are natural products.

  3. Fig. 3

    Between 1962 and 2000, no major classes of antibiotics were introduced.

  4. Fig. 4

    Surmounting resistance with scaffold alterations. Two ways of overcoming resistance are shown, using tetracycline (center) as an example. First, the tetracycline scaffold can be chemically modified, creating a tetracycline derivative like tigecycline that is no longer a substrate for the efflux pump (left). Second, a new scaffold like retapamulin, which is not a substrate for efflux and binds to a different site in the ribosome, can be used instead of tetracycline (right).

  5. Fig. 5

    The chemical structures of new and underexplored antibiotic scaffolds mentioned throughout the text are organized by type into three categories: synthetic, semisynthetic, and natural product. For synthetic and semisynthetic scaffolds, core scaffolds are shown in black and variable positions are shown in red.