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Antibiotics

Inactive but not inert

Nature Chemical Biology volume 6, pages 85–86 (2010)Cite this article

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Antibiotics can break down through the action of enzymes or through non-enzymatic processes. In the case of tetracycline, this drug 'debris' can have unexpected biological activities, including selection against resistance.

Antibiotic resistance is one of the principal threats to our ability to control infectious diseases. Resistance can take on many forms, but genetically encoded chemical modification and degradation of antibiotics are major contributors1. These mechanisms of resistance inevitably result in an accumulation of the chemical detritus of antibiotics in sites of infection and in the wider environment. In addition, environmental organisms are prodigious producers of antibiotics. Soil microbes in particular are spectacularly adept at producing these compounds. These antibiotics then decay because of intrinsic chemical instability and the metabolism, including resistance, of neighboring organisms. The biological impact of these 'inactivated' breakdown products of antibiotics has largely been ignored. This is a myopic view of the natural chemical world. There is growing evidence that antibiotics likely have a plethora of roles in addition to cell killing at high concentrations, and several studies have shown that sub-MIC (minimum inhibitory concentration) levels of antibiotics have pleiotropic effects on cellular networks2. Palmer et al.3 have directly investigated the roles of the breakdown products of the antibiotic tetracycline and show an unexpected link of these compounds with regulation of resistance.

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Figure 1: Antibiotic resistance is not neutral.

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  1. Department of Biochemistry and Biomedical Sciences, Gerard D. Wright is at the M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, Ontario, Canada.,

    Gerard D Wright

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Correspondence to Gerard D Wright.

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Wright, G. Inactive but not inert. Nat Chem Biol 6, 85–86 (2010). https://doi.org/10.1038/nchembio.299

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  • DOI: https://doi.org/10.1038/nchembio.299

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