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Antibiotics as probes of biological complexity

Nature Chemical Biology volume 7, pages 415–423 (2011)Cite this article

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Abstract

The utility of antibiotics has largely been based on their therapeutic application. However, in addition to clinical use, antibiotics have served as vital agents in probing bacterial complexity. Although not principally regarded as tools for dissecting bacterial genetics and biochemistry, antibiotics have nonetheless proved indispensable to understanding such essential functions as cell-wall biogenesis, DNA biosynthesis and the translation process. Herein we provide an overarching account of recent and landmark instances in which antibiotics have yielded critical information regarding many bacterial processes. We also elaborate on the importance of antibiotics and new chemical probes to the comprehension of genetic networks in the future. Given that antibiotics were among the first small molecules used to methodically perturb and understand biological systems, the past, present and future of antibiotics as probes of bacterial complexity offer some illustrative lessons for the broader field of chemical biology.

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Figure 1: Timeline of the discovery of antibiotics and their use as probes of bacterial complexity.
Figure 2: Chloramphenicol probes the stress response of cells during disruption of protein translocation.
Figure 3: A vancomycin photoaffinity probe identifies the mechanism of vancomycin resistance.
Figure 4: Cephalexin probes the relationship between divisome assembly and cell lysis.
Figure 5: Discovery of a new chemical probe of wall teichoic acid synthesis.
Figure 6: A chemical-genetic interaction network of seven antibiotics.

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Acknowledgements

E.D.B. acknowledges salary support from the Canada Research Chairs program and operating funds from the Canadian Institutes of Health Research (MOP-15496, MOP-64292 and MOP-81330) and Cystic Fibrosis Canada.

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Authors and Affiliations

  1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada

    Shannon B Falconer, Tomasz L Czarny & Eric D Brown

  2. Michael G. DeGroote Institute of Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada

    Shannon B Falconer, Tomasz L Czarny & Eric D Brown

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Correspondence to Eric D Brown.

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Falconer, S., Czarny, T. & Brown, E. Antibiotics as probes of biological complexity. Nat Chem Biol 7, 415–423 (2011). https://doi.org/10.1038/nchembio.590

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