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Signaling-mediated bacterial persister formation

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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References

  1. Balaban, N.Q. et al. Science 305, 1622–1625 (2004).

    Article  CAS  Google Scholar 

  2. Lewis, K. Nat. Rev. Microbiol. 5, 48–56 (2007).

    Article  CAS  Google Scholar 

  3. Smith, P.A. & Romesberg, F.E. Nat. Chem. Biol. 3, 549–556 (2007).

    Article  CAS  Google Scholar 

  4. Allison, K.R., Brynildsen, M.P. & Collins, J.J. Nature 473, 216–220 (2011).

    Article  CAS  Google Scholar 

  5. Levin, B.R. & Rozen, D.E. Nat. Rev. Microbiol. 4, 556–562 (2006).

    Article  CAS  Google Scholar 

  6. Gefen, O. & Balaban, N.Q. FEMS Microbiol. Rev. 33, 704–717 (2009).

    Article  CAS  Google Scholar 

  7. Keren, I. et al. FEMS Microbiol. Lett. 230, 13–18 (2004).

    Article  CAS  Google Scholar 

  8. Moyed, H.S. & Bertrand, K.P. J. Bacteriol. 155, 768–775 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Wang, X. & Wood, T.K. Appl. Environ. Microbiol. 77, 5577–5583 (2011).

    Article  CAS  Google Scholar 

  10. Wang, X. et al. Nat. Chem. Biol. 7, 359–366 (2011).

    Article  CAS  Google Scholar 

  11. Bassler, B.L. & Losick, R. Cell 125, 237–246 (2006).

    Article  CAS  Google Scholar 

  12. Wang, D., Ding, X.D. & Rather, P.N. J. Bacteriol. 183, 4210–4216 (2001).

    Article  CAS  Google Scholar 

  13. Martino, P.D. et al. Can. J. Microbiol. 49, 443–449 (2003).

    Article  Google Scholar 

  14. Lee, J. et al. ISME J. 2, 1007–1023 (2008).

    Article  CAS  Google Scholar 

  15. Han, T.H. et al. Res. Microbiol. 162, 108–116 (2010).

    Article  Google Scholar 

  16. Yanofsky, C., Horn, V. & Gollnick, P. J. Bacteriol. 173, 6009–6017 (1991).

    Article  CAS  Google Scholar 

  17. Piñero-Fernandez, S., Chimerel, C., Keyser, U.F. & Summers, D.K. J. Bacteriol. 193, 1793–1798 (2011).

    Article  Google Scholar 

  18. Garbe, T.R., Kobayashi, M. & Yukawa, H. Arch. Microbiol. 173, 78–82 (2000).

    Article  CAS  Google Scholar 

  19. Hirakawa, H. et al. Mol. Microbiol. 55, 1113–1126 (2005).

    Article  CAS  Google Scholar 

  20. Lee, H.H., Molla, M.N., Cantor, C.R. & Collins, J.J. Nature 467, 82–85 (2010).

    Article  CAS  Google Scholar 

  21. Weiner, L. & Model, P. Proc. Natl. Acad. Sci. USA 91, 2191–2195 (1994).

    Article  CAS  Google Scholar 

  22. Dukan, S. & Nystrom, T. J. Biol. Chem. 274, 26027–26032 (1999).

    Article  CAS  Google Scholar 

  23. Storz, G., Tartaglia, L.A. & Ames, B.N. Antonie Van Leeuwenhoek 58, 157–161 (1990).

    Article  CAS  Google Scholar 

  24. Crawford, D.R. & Davies, K.J. Environ. Health Perspect. 102 (suppl.), 25–28 (1994).

    PubMed  PubMed Central  Google Scholar 

  25. Rotem, E. et al. Proc. Natl. Acad. Sci. USA 107, 12541–12546 (2010).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

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

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

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Supplementary Movie 2

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Supplementary Movie 3

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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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