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Signaling-mediated bacterial persister formation

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Abstract

Here we show that bacterial communication through indole signaling induces persistence, a phenomenon in which a subset of an isogenic bacterial population tolerates antibiotic treatment. We monitor indole-induced persister formation using microfluidics and identify the role of oxidative-stress and phage-shock pathways in this phenomenon. We propose a model in which indole signaling 'inoculates' a bacterial subpopulation against antibiotics by activating stress responses, leading to persister formation.

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Figure 1: Indole induces persistence in E. coli.
Figure 2: Indole induces persistence through the phage-shock and OxyR pathways.

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Acknowledgements

We would like to thank R.H.W. Lam for help with microfluidics. This work was supported by funding from the US National Science Foundation, the US National Institutes of Health Director's Pioneer Award Program and the Howard Hughes Medical Institute.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Boston University, Boston, Massachusetts, USA

    Nicole M Vega, Kyle R Allison, Ahmad S Khalil & James J Collins

  2. Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA

    Nicole M Vega, Kyle R Allison, Ahmad S Khalil & James J Collins

  3. Center for BioDynamics, Boston University, Boston, Massachusetts, USA

    Nicole M Vega, Kyle R Allison, Ahmad S Khalil & James J Collins

  4. Boston University School of Medicine, Boston, Massachusetts, USA

    James J Collins

  5. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA

    James J Collins

Authors
  1. Nicole M Vega
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  2. Kyle R Allison
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  3. Ahmad S Khalil
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  4. James J Collins
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Contributions

N.M.V., K.R.A., A.S.K. and J.J.C. designed experiments, discussed results and contributed to the manuscript. N.M.V. performed all experiments. N.M.V., K.R.A. and A.S.K. analyzed data. A.S.K. developed the microfluidics platform and performed the microfluidic experiments.

Corresponding author

Correspondence to James J Collins.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Methods and Supplementary Results and Supplementary Note 1 (PDF 1456 kb)

Supplementary Movie 1

Vega_SuppMovie1 (MOV 53270 kb)

Supplementary Movie 2

Vega_SuppMovie2 (MOV 42497 kb)

Supplementary Movie 3

Vega_SuppMovie3 (MOV 53170 kb)

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Vega, N., Allison, K., Khalil, A. et al. Signaling-mediated bacterial persister formation. Nat Chem Biol 8, 431–433 (2012). https://doi.org/10.1038/nchembio.915

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