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Collective antibiotic tolerance: mechanisms, dynamics and intervention

Nature Chemical Biology volume 11, pages 182–188 (2015)Cite this article

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Abstract

Bacteria have developed resistance against every antibiotic at a rate that is alarming considering the timescale at which new antibiotics are developed. Thus, there is a critical need to use antibiotics more effectively, extend the shelf life of existing antibiotics and minimize their side effects. This requires understanding the mechanisms underlying bacterial drug responses. Past studies have focused on survival in the presence of antibiotics by individual cells, as genetic mutants or persisters. Also important, however, is the fact that a population of bacterial cells can collectively survive antibiotic treatments lethal to individual cells. This tolerance can arise by diverse mechanisms, including resistance-conferring enzyme production, titration-mediated bistable growth inhibition, swarming and interpopulation interactions. These strategies can enable rapid population recovery after antibiotic treatment and provide a time window during which otherwise susceptible bacteria can acquire inheritable genetic resistance. Here, we emphasize the potential for targeting collective antibiotic tolerance behaviors as an antibacterial treatment strategy.

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Figure 1: Bacterial survival modes.
Figure 2: Comparison of population-level responses due to different forms of CAT or persistence.
Figure 3: Underlying mechanisms of CAT.
Figure 4: Inhibition strategies.

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Acknowledgements

Research in our lab related to the topic of this article is in part funded by the US National Institutes of Health, National Science Foundation and Army Research Office and by the David and Lucile Packard Foundation. H.R.M. acknowledges the National Science Foundation Graduate Research Fellowship Program; J.K.S. acknowledges a Duke Center for Biomolecular and Tissue Engineering graduate fellowship; and A.J. Lopatkin acknowledges the Howard G. Clark fellowship.

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  1. Hannah R Meredith and Jaydeep K Srimani: These authors contributed equally to this work.

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  1. Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA

    Hannah R Meredith, Jaydeep K Srimani, Anna J Lee, Allison J Lopatkin & Lingchong You

  2. Center for Systems Biology, Duke University, Durham, North Carolina, USA

    Lingchong You

  3. Center for Genomic and Computational Biology, Duke University, Durham, North Carolina, USA

    Lingchong You

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Meredith, H., Srimani, J., Lee, A. et al. Collective antibiotic tolerance: mechanisms, dynamics and intervention. Nat Chem Biol 11, 182–188 (2015). https://doi.org/10.1038/nchembio.1754

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