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A cell-cell communication signal integrates quorum sensing and stress response

Nature Chemical Biology volume 9, pages 339–343 (2013)Cite this article

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An Erratum to this article was published on 20 May 2013

This article has been updated

Abstract

Pseudomonas aeruginosa uses a hierarchical quorum sensing (QS) network consisting of las, pqs and rhl regulatory elements to coordinate the expression of bacterial virulence genes. However, clinical isolates frequently contain loss-of-function mutations in the central las system. This motivated us to search for a mechanism that may functionally substitute las. Here we report identification of a new QS signal, IQS. Disruption of IQS biosynthesis paralyzes the pqs and rhl QS systems and attenuates bacterial virulence. Production of IQS is tightly controlled by las under normal culture conditions but is also activated by phosphate limitation, a common stressor that bacteria encounter during infections. Thus, these results have established an integrated QS system that connects the central las system and phosphate-stress response mechanism to the downstream pqs and rhl regulatory systems. Our discovery highlights the complexity of QS signaling systems and extends the gamut of QS and stress-response mechanisms.

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Figure 1: Effect of ambB mutation on the production of virulence factors and QS signals in P. aeruginosa in LB medium.
Figure 2: Purification and structural analysis of IQS.
Figure 3: Production of QS signals C4HSL and PQS is dependent on IQS.
Figure 4: Coregulation of ambBCDE expression and IQS production by las and the phosphate-depletion stress response mechanism.
Figure 5: Impact of IQS on bacterial virulence and in vivo survival.

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Change history

  • 12 April 2012

    In the version of this article initially published online, the IQS structure used in Figure 2c and in the graphical abstract was incorrect. The error has been corrected for the PDF and HTML versions of this article.

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Acknowledgements

This work was supported by the Biomedical Research Council, Agency of Science, Technology and Research (A*Star), Singapore.

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Author notes

  1. Jasmine Lee and Jien Wu: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Molecular and Cell Biology, Proteos, Singapore

    Jasmine Lee, Jien Wu, Yinyue Deng, Jing Wang, Chao Wang, Jianhe Wang, Changqing Chang, Yihu Dong & Lian-Hui Zhang

  2. School of Molecular Medical Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, UK

    Paul Williams

  3. Department of Biological Sciences, National University of Singapore, Singapore

    Lian-Hui Zhang

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Contributions

J.L. performed all experiments except those described below. J. Wu performed IQS purification and structural analysis. Y.D. and P.W. assisted in reporter strain construction and data analysis. Jianhe Wang and Jing Wang assisted in virulence assays. C.W. conducted bioinformatics analysis. C.C. performed RT-PCR analysis. Y.D. generated mutant strains and conducted phenotype analysis. J.L., J. Wu and L.-H.Z. designed experiments, analyzed data and wrote the paper.

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Correspondence to Lian-Hui Zhang.

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Lee, J., Wu, J., Deng, Y. et al. A cell-cell communication signal integrates quorum sensing and stress response. Nat Chem Biol 9, 339–343 (2013). https://doi.org/10.1038/nchembio.1225

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