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Antibiotic Discovery and Development pp 33–75Cite as

Rational Approaches to Antibacterial Discovery: Pre-Genomic Directed and Phenotypic Screening

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Abstract

After the discovery of antibacterial chemicals and antibiotics through the 1950s by empirical assays based on growth inhibition, methods gradually evolved to encompass more directed screens. These were initially based upon the phenomena revealed by the action of previously discovered antibiotics and served the dual purpose of exploiting bacterial-selective pathways and aiding in recognition of novelty among natural product samples (dereplication). Later, as microbial genetics began to uncover the range of essential bacterial genes and provide tools for construction of test strains, targeted whole cell screening for antibacterials took on more of the characteristics of a hunt for genetic mutations by exploiting the expected phenotypes of desired inhibitors. Although these methods initially succeeded in expanding the repertoire of useful classes of antibiotics inhibiting cell wall synthesis, no marketed novel non-cell wall targeted antibacterial classes have been found through these methods, nor have they been found via the later genomically based targeted screening that followed. Possible reasons for this low output are speculated upon.

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    Lynn L. Silver

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Silver, L.L. (2012). Rational Approaches to Antibacterial Discovery: Pre-Genomic Directed and Phenotypic Screening. In: Dougherty, T., Pucci, M. (eds) Antibiotic Discovery and Development. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-1400-1_2

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