Antibiotics are often unstable and can decay into various compounds with potential biological activities. We found that as tetracycline degrades, the competitive advantage conferred to bacteria by resistance not only diminishes but actually reverses to become a prolonged disadvantage due to the activities of more stable degradation products. Tetracycline decay can lead to net selection against resistance, which may help explain the puzzling coexistence of sensitive and resistant strains in natural environments.
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We thank R. Lenski (Michigan State University) for the gift of plasmids, and we thank R. Chait, D. Kahne and F. Solomon for helpful insights and R. Ward and M. Elowitz for comments on the manuscript. This work was supported in part by the Bill and Melinda Gates Foundation through the Grand Challenges Exploration Initiative, US National Institutes of Health grant R01 GM081617 (to R.K.) and a George Murray Scholarship (to A.C.P.).
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Palmer, A., Angelino, E. & Kishony, R. Chemical decay of an antibiotic inverts selection for resistance. Nat Chem Biol 6, 105–107 (2010). https://doi.org/10.1038/nchembio.289
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