Article | Published:

Eavesdropping and crosstalk between secreted quorum sensing peptide signals that regulate bacteriocin production in Streptococcus pneumoniae

The ISME Journal (2018) | Download Citation

Abstract

Quorum sensing (QS), where bacteria secrete and respond to chemical signals to coordinate population-wide behaviors, has revealed that bacteria are highly social. Here, we investigate how diversity in QS signals and receptors can modify social interactions controlled by the QS system regulating bacteriocin secretion in Streptococcus pneumoniae, encoded by the blp operon (bacteriocin-like peptide). Analysis of 4096 pneumococcal genomes detected nine blp QS signals (BlpC) and five QS receptor groups (BlpH). Imperfect concordance between signals and receptors suggested widespread social interactions between cells, specifically eavesdropping (where cells respond to signals that they do not produce) and crosstalk (where cells produce signals that non-clones detect). This was confirmed in vitro by measuring the response of reporter strains containing six different blp QS receptors to cognate and non-cognate peptides. Assays between pneumococcal colonies grown adjacent to one another provided further evidence that crosstalk and eavesdropping occur at endogenous levels of signal secretion. Finally, simulations of QS strains producing bacteriocins revealed that eavesdropping can be evolutionarily beneficial even when the affinity for non-cognate signals is very weak. Our results highlight that social interactions can mediate intraspecific competition among bacteria and reveal that competitive interactions can be modified by polymorphic QS systems.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol. 2001;55:165–99.

  2. 2.

    Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319–46.

  3. 3.

    Bassler BL, Greenberg EP, Stevens AM. Cross-species induction of luminescence in the quorum-sensing bacterium Vibrio harveyi. J Bacteriol. 1997;179:4043–5.

  4. 4.

    Redfield RJ. Is quorum sensing a side effect of diffusion sensing? Trends Microbiol. 2002;10:365–70.

  5. 5.

    Schluter J, Schoech AP, Foster KR, Mitri S. The evolution of quorum sensing as a mechanism to infer kinship. PLoS Comput Biol. 2016;12:e1004848.

  6. 6.

    West SA, Griffin AS, Gardner A, Diggle SP. Social evolution theory for microorganisms. Nat Rev Microbiol. 2006;4:597–607.

  7. 7.

    Crespi BJ. The evolution of social behavior in microorganisms. Trends Ecol Evol. 2001;16:178–83.

  8. 8.

    Atkinson S, Williams P. Quorum sensing and social networking in the microbial world. J R Soc. 2009;6:959–78.

  9. 9.

    Ansaldi M, Dubnau D. Diversifying selection at the Bacillus quorum-sensing locus and determinants of modification specificity during synthesis of the ComX pheromone. J Bacteriol. 2004;186:15–21.

  10. 10.

    Ji G, Beavis R, Novick RP. Bacterial interference caused by autoinducing peptide variants. Science. 1997;276:2027–30.

  11. 11.

    Swem LR, Swem DL, Wingreen NS, Bassler BL. Deducing receptor signaling parameters from in vivo analysis: LuxN/AI-1 quorum sensing in Vibrio harveyi. Cell. 2008;134:461–73.

  12. 12.

    Bouillaut L, Perchat S, Arold S, Zorrilla S, Slamti L, Henry C, et al. Molecular basis for group-specific activation of the virulence regulator PlcR by PapR heptapeptides. Nucleic Acids Res. 2008;36:3791–801.

  13. 13.

    Jiricny N, Diggle SP, West SA, Evans BA, Ballantyne G, Ross-Gillespie A, et al. Fitness correlates with the extent of cheating in a bacterium. J Evol Biol. 2010;23:738–47.

  14. 14.

    Strassmann JE, Queller DC. Evolution of cooperation and control of cheating in a social microbe. Proc Natl Acad Sci USA. 2011;108:10855–62.

  15. 15.

    Diggle SP, Griffin AS, Campbell GS, West SA. Cooperation and conflict in quorum-sensing bacterial populations. Nature. 2007;450:411–4.

  16. 16.

    Regev-Yochay G, Raz M, Dagan R, Porat N, Shainberg B, Pinco E, et al. Nasopharyngeal carriage of Streptococcus pneumoniae by adults and children in community and family settings. Clin Infect Dis. 2004;38:632–9.

  17. 17.

    Wyllie AL, Chu MLJN, Schellens MHB, Gastelaars JVE, Jansen MD, Van Der Ende A, et al. Streptococcus pneumoniae in saliva of Dutch primary school children. PLoS ONE. 2014;9:1–8.

  18. 18.

    García-Rodríguez JA, Fresnadillo Martínez MJ. Dynamics of nasopharyngeal colonization by potential respiratory pathogens. J Antimicrob Chemother. 2002;50:59–73.

  19. 19.

    Sauver JS, Marrs CF, Foxman B, Somsel P, Madera R, Gilsdorf JR. Risk factors for otitis media and carriage of multiple strains of Haemophilus influenzae and Streptococcus pneumoniae. Emerg Infect Dis. 2000;6:622–30.

  20. 20.

    Brugger SD, Frey P, Aebi S, Hinds J, Muhlemann K. Multiple colonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal polysaccharide vaccine. PLoS ONE. 2010;5:e11638.

  21. 21.

    Meats E, Brueggemann AB, Enright MC, Sleeman K, Griffiths DT, Crook DW, et al. Stability of serotypes during nasopharyngeal carriage of Streptococcus pneumoniae. J Clin Microbiol. 2003;41:386–92.

  22. 22.

    Turner P, Turner C, Jankhot A, Helen N, Lee SJ, Day NP, et al. A longitudinal study of Streptococcus pneumoniae carriage in a cohort of infants and their mothers on the Thailand-Myanmar border. PLoS ONE. 2012;7. https://doi.org/10.1371/journal.pone.0038271.

  23. 23.

    Dawid S, Roche AM, Weiser JN. The blp bacteriocins of Streptococcus pneumoniae mediate intraspecies competition both in vitro and in vivo. Infect Immun. 2007;75:443–51.

  24. 24.

    Lux T, Nuhn M, Hakenbeck R, Reichmann P. Diversity of bacteriocins and activity spectrum in Streptococcus pneumoniae. J Bacteriol. 2007;189:7741–51.

  25. 25.

    Miller EL, Abrudan MI, Roberts IS, Rozen DE. Diverse ecological strategies are encoded by Streptococcus pneumoniae bacteriocin-like peptides. Genome Biol Evol. 2016;8:1072–90.

  26. 26.

    De Saizieu A, Gardes C, Flint N, Wagner C, Kamber M, Mitchell TJ, et al. Microarray-based identification of a novel Streptococcus pneumoniae regulon controlled by an autoinduced peptide. J Bacteriol. 2000;182:4696–703.

  27. 27.

    Reichmann P, Hakenbeck R. Allelic variation in a peptide-inducible two-component system of Streptococcus pneumoniae. FEMS Microbiol Lett. 2000;190:231–6.

  28. 28.

    Kjos M, Miller E, Slager J, Lake FB, Gericke O, Roberts IS, et al. Expression of Streptococcus pneumoniae bacteriocins is induced by antibiotics via regulatory interplay with the competence system. PLoS Pathog. 2016;12:e1005422.

  29. 29.

    Håvarstein LS, Diep DB, Nes IF. A family of bacteriocin ABC transporters carry out proteolytic processing of their substrates concomitant with export. Mol Microbiol. 1995;16:229–40.

  30. 30.

    Wholey W-Y, Kochan TJ, Storck DN, Dawid S. Coordinated bacteriocin expression and competence in Streptococcus pneumoniae contributes to genetic adaptation through neighbor predation. PLoS Pathog. 2016;12:e1005413.

  31. 31.

    Iannelli F, Oggioni MR, Pozzi G. Sensor domain of histidine kinase ComD confers competence pherotype specificity in Streptoccoccus pneumoniae. FEMS Microbiol Lett. 2005;252:321–6.

  32. 32.

    Miller EL, Evans BA, Cornejo OE, Roberts IS, Rozen D. Pherotype polymorphism in Streptococcus pneumoniae has no obvious effects on population structure and recombination. Genome Biol Evol. 2017;9:2546–59.

  33. 33.

    Pinchas MD, LaCross NC, Dawid S. An electrostatic interaction between BlpC and BlpH dictates pheromone specificity in the control of bacteriocin production and immunity in Streptococcus pneumoniae. J Bacteriol. 2015;197:1236–48.

  34. 34.

    Eldar A. Social conflict drives the evolutionary divergence of quorum sensing. Proc Natl Acad Sci USA. 2011;108:13635–40.

  35. 35.

    Pollak S, Omer-Bendori S, Even-Tov E, Lipsman V, Bareia T, Ben-Zion I, et al. Facultative cheating supports the coexistence of diverse quorum-sensing alleles. Proc Natl Acad Sci USA. 2016;113:2152–7.

  36. 36.

    Son MR, Shchepetov M, Adrian P V, Madhi SA, de Gouveia L, von Gottberg A, et al. Conserved mutations in the pneumococcal bacteriocin transporter gene, blpA, result in a complex population consisting of producers and cheaters. MBio. 2012;2. https://doi.org/10.1128/mBio.00179-11.

  37. 37.

    Chewapreecha C, Harris SR, Croucher NJ, Turner C, Marttinen P, Cheng L, et al. Dense genomic sampling identifies highways of pneumococcal recombination. Nat Genet. 2014;46:305–9.

  38. 38.

    Croucher NJ, Finkelstein JA, Pelton SI, Mitchell PK, Lee GM, Parkhill J, et al. Population genomics of post-vaccine changes in pneumococcal epidemiology. Nat Genet. 2013;45:656–63.

  39. 39.

    Chancey ST, Agrawal S, Schroeder MR, Farley MM, Tettelin HH, Stephens DS. Composite mobile genetic elements disseminating macrolide resistance in Streptococcus pneumoniae. Front Microbiol. 2015;6:1–14.

  40. 40.

    Bogaert D, Engelen MN, Timmers-Reker AJM, Elzenaar KP, Peerbooms PGH, Coutinho RA, et al. Pneumococcal carriage in children in the Netherlands: a molecular epidemiological study. J Clin Microbiol. 2001;39:3316–20.

  41. 41.

    McGee L, McDougal L, Zhou J, Spratt BG, Tenover FC, George R, et al. Nomenclature of major antimicrobial-resistant clones of Streptococcus pneumoniae defined by the pneumococcal molecular epidemiology network. J Clin Microbiol. 2001;39:2565–71.

  42. 42.

    Croucher NJ, Harris SR, Fraser C, Quail MA, Burton J, van der Linden M, et al. Rapid pneumococcal evolution in response to clinical interventions. Science. 2011;331:430–4.

  43. 43.

    Croucher NJ, Mitchell AM, Gould KA, Inverarity D, Barquist L, Feltwell T, et al. Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection. PLoS Genet. 2013;9. https://doi.org/10.1371/journal.pgen.1003868.

  44. 44.

    Moreno-Gamez S, Sorg R, Kjos M, Weissing F, van Doorn GS, Veening J. Quorum sensing integrates environmental cues, cell density and cell history to control bacterial competence. bioRxiv. 2016;31:75762.

  45. 45.

    Slager J, Kjos M, Attaiech L, Veening J-W. Antibiotic-induced replication stress triggers bacterial competence by increasing gene dosage near the origin. Cell. 2014;157:395–406.

  46. 46.

    Kümmerli R, Brown SP. Molecular and regulatory properties of a public good shape the evolution of cooperation. Proc Natl Acad Sci USA. 2010;107:18921–6.

  47. 47.

    Yang J, Evans BA, Rozen DE. Signal diffusion and the mitigation of social exploitation in pneumococcal competence signalling. Proc R Soc B Biol Sci. 2010;277:2991–9.

  48. 48.

    Ruparell A, Dubern JF, Ortori CA, Harrison F, Halliday NM, Emtage A, et al. The fitness burden imposed by synthesizing quorum sensing signals. Sci Rep. 2016;6:33101.

  49. 49.

    Valente C, Dawid S, Pinto FR, Hinds J, Simões AS, Gould KA, et al. The blp locus of Streptococcus pneumoniae plays a limited role in the selection of strains that can cocolonize the human nasopharynx. Appl Environ Microbiol. 2016;82:5206–15.

  50. 50.

    West SA, Winzer K, Gardner A, Diggle SP. Quorum sensing and the confusion about diffusion. Trends Microbiol. 2012;20:586–94.

  51. 51.

    Zhang F, Kwan A, Xu A, Süel GM. A synthetic quorum sensing system reveals a potential private benefit for public good production in a biofilm. PLoS ONE. 2015;10:15–9.

  52. 52.

    Stefanic P, Decorosi F, Viti C, Petito J, Cohan FM, Mandic-Mulec I. The quorum sensing diversity within and between ecotypes of Bacillus subtilis. Environ Microbiol. 2012;14:1378–89.

Download references

Acknowledgements

We would like to thank Frank Lake for technical assistance. This work was supported by the Biotechnology and Biological Sciences Research Council (Grant Number BB/J006009/1) to DER and ISR and by the Wellcome Trust (105610/Z/14/Z) to the University of Manchester. MA is supported by the Biotechnology and Biological Sciences Research Council (Grant Number BB/M000281/1). Work in the Veening lab is supported by the EMBO Young Investigator Program, a VIDI fellowship (864.12.001) from the Netherlands Organisation for Scientific Research, Earth and Life Sciences (NWO-ALW) and ERC starting grant 337399-PneumoCell. MK is supported by a grant from The Research Council of Norway (250976/F20).

Author information

Author notes

  1. These authors contributed equally: Eric L. Miller, Morten Kjos.

Affiliations

  1. School of Biological Science, Faculty of Biology, Medicine, and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, M13 9PL, UK

    • Eric L. Miller
    •  & Ian S. Roberts
  2. Institute of Biology Leiden, Leiden University, Leiden, 2333 BE, The Netherlands

    • Eric L. Miller
    •  & Daniel E. Rozen
  3. Molecular Genetics Group, Groningen Biomolecular Sciences and Biotechnology Institute, Centre for Synthetic Biology, University of Groningen, Groningen, 9700 AE, The Netherlands

    • Morten Kjos
    •  & Jan-Willem Veening
  4. Faculty of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, 1432, Ås, Norway

    • Morten Kjos
  5. Wellcome Trust Sanger Institute, Genome Campus, Cambridge, CB10 1SA, UK

    • Monica I. Abrudan
  6. Faculty of Medicine, School of Public Health, Imperial College, London, W2 1PG, UK

    • Monica I. Abrudan
  7. Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Biophore Building, 1015, Lausanne, Switzerland

    • Jan-Willem Veening

Authors

  1. Search for Eric L. Miller in:

  2. Search for Morten Kjos in:

  3. Search for Monica I. Abrudan in:

  4. Search for Ian S. Roberts in:

  5. Search for Jan-Willem Veening in:

  6. Search for Daniel E. Rozen in:

Conflict of interest

The authors declare that they have no conflict of interest.

Corresponding authors

Correspondence to Ian S. Roberts or Jan-Willem Veening or Daniel E. Rozen.

Electronic supplementary material

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/s41396-018-0178-x