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A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation

An Erratum to this article was published on 19 September 2017

An Erratum to this article was published on 19 September 2017

An Erratum to this article was published on 17 May 2017

This article has been updated

Abstract

Quorum sensing (QS) is a cell–cell communication process that enables bacteria to track cell population density and orchestrate collective behaviors. QS relies on the production and detection of, and the response to, extracellular signal molecules called autoinducers. In Vibrio cholerae, multiple QS circuits control pathogenesis and biofilm formation. Here, we identify and characterize a new QS autoinducer–receptor pair. The autoinducer is 3,5-dimethylpyrazin-2-ol (DPO). DPO is made from threonine and alanine, and its synthesis depends on threonine dehydrogenase (Tdh). DPO binds to and activates a transcription factor, VqmA. The VqmA–DPO complex activates expression of vqmR, which encodes a small regulatory RNA. VqmR represses genes required for biofilm formation and toxin production. We propose that DPO allows V. cholerae to regulate collective behaviors to, among other possible roles, diversify its QS output during colonization of the human host.

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Figure 1: VqmR production is regulated by an extracellular activity.
Figure 2: Threonine dehydrogenase (Tdh) is required for VqmA activation.
Figure 3: The autoinducer that controls VqmA activity is produced from threonine.
Figure 4: Identification and proposed biosynthesis of DPO.
Figure 5: DPO induces production of VqmR, which represses V. cholerae biofilm formation.
Figure 6: DPO-dependent and independent QS pathways in V. cholerae.

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Change history

  • 04 April 2017

    In the version of this article initially published, the compound structure immediately upstream of DPO in the biosynthetic scheme in Figure 4e was redrawn incorrectly during production. The structure was missing a methyl group. The error has been corrected in the HTML and PDF versions of the article.

  • 23 August 2017

    In the version of this article initially published, the trace shown in Figure 4b was mislabeled as the RNA VqmR instead of the protein VqmA. The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

This work was supported by the Howard Hughes Medical Institute, NIH Grant 2R37GM065859, and National Science Foundation Grant MCB-0948112 (to B.L.B.). K.P. was supported by a career development award from the Human Frontiers Science Program (CDA00024/2016-C) and DFG Grant PA2820/1. J.E.S. was supported by the Department of Defense (DoD) through the National Defense Science and Engineering Graduate Fellowship (NDSEG) program. M.R.S. gratefully acknowledges support from the Pew Biomedical Scholars Program. K.R.S. was supported by the Eli Lilly–Edward C. Taylor Fellowship in Chemistry. We thank the members of the Bassler lab for helpful discussions. We especially thank M. Donia, T. Srikumar, I. Pelczer, and S. Kyin for help in initial analyses of DPO.

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K.P., J.E.S., M.R.S. and B.L.B. designed the experiments and K.P., J.E.S., K.R.S., J.-P.C. and M.R.S. performed the experiments. Specifically, K.P., J.E.S. and J.P.S. performed northern and western blot experiments; K.P., J.E.S., K.R.S. and M.R.S. were involved in the autoinducer-capture experiments; K.P., J.E.S., K.R.S., J.P.S., M.R.S. and B.L.B. analyzed the data; and K.P., J.E.S., M.R.S. and B.L.B. wrote the paper.

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Correspondence to Bonnie L Bassler.

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Papenfort, K., Silpe, J., Schramma, K. et al. A Vibrio cholerae autoinducer–receptor pair that controls biofilm formation. Nat Chem Biol 13, 551–557 (2017). https://doi.org/10.1038/nchembio.2336

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