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Pneumococcal quorum sensing drives an asymmetric owner–intruder competitive strategy during carriage via the competence regulon

Nature Microbiology volume 4, pages 198–208 (2019)Cite this article

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Abstract

Competition among microorganisms is a key determinant of successful host colonization and persistence. For Streptococcus pneumoniae, lower than predicted rates of co-colonizing strains suggest a competitive advantage for resident bacteria over newcomers. In light of evolutionary theory, we hypothesized that S. pneumoniae use owner–intruder asymmetries to settle contests, leading to the disproportionate success of the initial resident ‘owner’, regardless of the genetic identity of the ‘intruder’. We investigated the determinants of within-host competitive success utilizing S. pneumoniae colonization of the upper respiratory tract of infant mice. Within 6 h, colonization by the resident inhibited colonization by an isogenic challenger. The competitive advantage of the resident was dependent on quorum sensing via the competence (Com) regulon and downstream choline binding protein D (CbpD) and on the competence-induced bacteriocins A and B (CibAB) implicated in fratricide. CbpD and CibAB are highly conserved across pneumococcal lineages, indicating evolutionary advantages for asymmetric competitive strategies within the species. Mathematical modelling supported a significant role for quorum sensing via the Com regulon in competition, even for strains with different competitive advantages. Our study suggests that asymmetric owner–intruder competitive strategies do not require complex cognition and are used by a major human pathogen to determine ‘ownership’ of human hosts.

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Fig. 1: The resident prevails in asymmetric pneumococcal competition for colonization.
Fig. 2: Asymmetric competition is dependent on direct interactions between resident and challenger pneumococci.
Fig. 3: Prevention of challenger colonization is dependent on QS in the resident and competence-induced fratricide.
Fig. 4: Predictions of winners between resident and challenger from the mathematical model.

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Data availability

The in vivo measurements, formatted as used to fit the competition model, are available on figshare at https://doi.org/10.6084/m9.figshare.7166432. The code used to run and fit the population dynamics model, and draw the associated plots, is available at github: https://github.com/johnlees/competition_model (Apache 2.0 license). The code we used to calculate Tajima’s D is available at github: https://github.com/johnlees/tajima-D (GPL 2.0 license). The data that support the findings of this study are available from the corresponding author upon request.

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Acknowledgements

The authors thank S. Frost and J. Corander for their advice on the formulation of the stochastic model and likelihood-free model fitting, respectively.

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Authors and Affiliations

  1. Department of Microbiology, New York University School of Medicine, New York, NY, USA

    Pamela Shen, John A. Lees, Gavyn Chern Wei Bee & Jeffrey N. Weiser

  2. School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA

    Sam P. Brown

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Contributions

P.S. contributed to project design, experimental work, data analyses and interpretation, and drafting of the manuscript. J.A.L. designed mathematical modelling, carried out all simulations and population genomics, interpreted data, and prepared the modelling section of the manuscript. G.C.W.B. assisted with experimental work. S.P.B. provided assistance on mathematical modelling and drafting of the manuscript. J.N.W. is the corresponding author and oversaw the project conception and design, data interpretation, and manuscript preparation.

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Correspondence to Jeffrey N. Weiser.

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Supplementary Information

Supplementary Methods, Supplementary Figures 1–13, Supplementary Tables 1–3, 5 and 6, and Supplementary References.

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Supplementary Table 4

Conservation of bacteriocins in the pneumococcal population.

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Shen, P., Lees, J.A., Bee, G.C.W. et al. Pneumococcal quorum sensing drives an asymmetric owner–intruder competitive strategy during carriage via the competence regulon. Nat Microbiol 4, 198–208 (2019). https://doi.org/10.1038/s41564-018-0314-4

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