Bacterial cell–cell signalling, or quorum sensing, is characterized by the secretion and groupwide detection of small diffusible signal molecules called autoinducers. This mechanism allows cells to coordinate their behaviour in a density-dependent manner. A quorum-sensing cell may directly respond to the autoinducers it produces in a cell-autonomous and quorum-independent manner, but the strength of this self-sensing effect and its impact on bacterial physiology are unclear. Here, we explore the existence and impact of self-sensing in the Bacillus subtilis ComQXP and Rap-Phr quorum-sensing systems. By comparing the quorum-sensing response of autoinducer-secreting and non-secreting cells in co-culture, we find that secreting cells consistently show a stronger response than non-secreting cells. Combining genetic and quantitative analyses, we demonstrate this effect to be a direct result of self-sensing and rule out an indirect regulatory effect of the autoinducer production genes on response sensitivity. In addition, self-sensing in the ComQXP system affects persistence to antibiotic treatment. Together, these findings indicate the existence of self-sensing in the two most common designs of quorum-sensing systems of Gram-positive bacteria.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $5.17 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Waters, C. M. & Bassler, B. L. Quorum sensing: cell-to-cell communication in bacteria. Annu. Rev. Cell Dev. Biol. 21, 319–346 (2005).
Berg, H. C. Random Walks in Biology (Princeton Univ. Press, Princeton, 1993).
Doğaner, B. A., Yan, L. K. & Youk, H. Autocrine signaling and quorum sensing: extreme ends of a common spectrum. Trends Cell. Biol. 26, 262–271 (2016).
Youk, H. & Lim, W. A. Secreting and sensing the same molecule allows cells to achieve versatile social behaviors. Science 343, 1242782 (2014).
Pottathil, M. & Lazazzera, B. A. The extracellular Phr peptide-Rap phosphatase signaling circuit of Bacillus subtilis. Front. Biosci. 8, d32–45 (2003).
Grossman, A. D. Genetic networks controlling the initiation of sporulation and the development of genetic competence in Bacillus subtilis.Annu. Rev. Genet. 29, 477–508 (1995).
Comella, N. & Grossman, A. D. Conservation of genes and processes controlled by the quorum response in bacteria: characterization of genes controlled by the quorum-sensing transcription factor ComA in Bacillus subtilis. Mol. Microbiol. 57, 1159–1174 (2005).
Yüksel, M. et al. Fitness trade-offs in competence differentiation of Bacillus subtilis. Front. Microbiol. 7, 888 (2016).
Johnsen, P. J., Dubnau, D. & Levin, B. R. Episodic selection and the maintenance of competence and natural transformation in Bacillus subtilis. Genetics 181, 1521–1533 (2009).
Magnuson, R., Solomon, J. & Grossman, A. D. Biochemical and genetic characterization of a competence pheromone from B. subtilis. Cell 77, 207–216 (1994).
Bacon, S. K., Palmer, T. M. & Grossman, A. D. Characterization of comQ and comX, two genes required for production of ComX Pheromone in Bacillus subtilis. J. Bacteriol. 184, 410–419 (2002).
Ansaldi, M. et al. Specific activation of the Bacillus quorum-sensing systems by isoprenylated pheromone variants. Mol. Microbiol. 44, 1561–1573 (2002).
Piazza, F., Tortosa, P. & Dubnau, D. Mutational analysis and membrane topology of ComP, a quorum-sensing histidine kinase of Bacillus subtilis controlling competence development. J. Bacteriol. 181, 4540–4548 (1999).
Oslizlo, A. et al. Private link between signal and response in Bacillus subtilis quorum sensing. Proc. Natl Acad. Sci. USA 111, 1586–1591 (2014).
Tortosa, P. et al. Specificity and genetic polymorphism of the Bacillus competence quorum-sensing system. J. Bacteriol. 183, 451–460 (2001).
Msadek, T. et al. DegS-DegU and ComP-ComA modulator-effector pairs control expression of the Bacillus subtilis pleiotropic regulatory gene degQ. J. Bacteriol. 173, 2366–2377 (1991).
Bendori, S. O. et al. The RapP-PhrP quorum-sensing system of Bacillus subtilis strain NCIB3610 affects biofilm formation through multiple targets, due to an atypical signal-insensitive allele of RapP. J. Bacteriol. 197, 592–602 (2015).
Parashar, V. et al. A plasmid-encoded phosphatase regulates Bacillus subtilis biofilm architecture, sporulation, and genetic competence. J. Bacteriol. 195, 2437–2448 (2013).
Pollak, S., Omer Bendori, S. & Eldar, A. A complex path for domestication of B. subtilis sociality. Curr. Genet. 61, 493–496 (2015).
Baker, M. D. & Neiditch, M. B. Structural basis of response regulator inhibition by a bacterial anti-activator protein. PLoS Biol. 9, 2624 (2011).
Lazazzera, B. A., Solomon, J. M. & Grossman, A. D. An exported peptide functions intracellularly to contribute to cell density signaling in B. subtilis. Cell 89, 917–925 (1997).
Lazazzera, B. A. et al. An autoregulatory circuit affecting peptide signaling in Bacillus subtilis. J. Bacteriol. 181, 5193–5200 (1999).
Drees, B. et al. A modular view of the diversity of cell-density-encoding schemes in bacterial quorum-sensing systems. Biophys. J. 107, 266–277 (2014).
Even-Tov, E. et al. Social evolution selects for redundancy in bacterial quorum sensing. PLoS Biol. 14, e1002386 (2016).
Schuster, M. et al. Acyl-homoserine lactone quorum sensing: from evolution to application. Annu. Rev. Microbiol. 67, 43–63 (2013).
Schuster, M., Sexton, D. J. & Hense, B. A. Why quorum sensing controls private goods. Front. Microbiol. 8, 885 (2017).
Gore, J., Youk, H. & van Oudenaarden, A. Snowdrift game dynamics and facultative cheating in yeast. Nature 459, 253–256 (2009).
Koschwanez, J. H., Foster, K. R. & Murray, A. W. Sucrose utilization in budding yeast as a model for the origin of undifferentiated multicellularity. PLoS Biol. 9, e1001122 (2011).
Ratzke, C. & Gore, J. Self-organized patchiness facilitates survival in a cooperatively growing Bacillus subtilis population. Nat. Microbiol. 1, 16022 (2016).
Hense, B. A. et al. Does efficiency sensing unify diffusion and quorum sensing? Nat. Rev. Microbiol. 5, 230–239 (2007).
Harwood, C. R. & Cutting, S. M. (eds) Molecular Biological Methods for Bacillus (Wiley, Chichester, 1990).
This work was supported by European Research Council grants 281301 and 724805. The authors thank R.D. Oshri and N. Antonovsky for comments and N. Sigal for help with qPCR.
The authors declare no competing financial interests.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Supplementary Figures 1–10, Supplementary Tables 1 and 2, Supplementary Discussion, Supplementary References.
Supplementary Dataset 1Description: Zip file including 11 excel files. These files include all data used in the manuscript figures and supplementary figures. File name corresponds to the figure numbers whose data it includes.
About this article
Journal of Molecular Biology (2019)
Journal of Molecular Biology (2019)
PLOS Computational Biology (2019)
Frontiers in Cellular and Infection Microbiology (2019)
The State of the Union Is Strong: a Review of ASM's 6th Conference on Cell-Cell Communication in Bacteria
Journal of Bacteriology (2018)