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Ecological and stochastic determinants of the growth and persistence of the oral pathogen Porphyromonas gingivalis
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  • Published: 26 February 2026

Ecological and stochastic determinants of the growth and persistence of the oral pathogen Porphyromonas gingivalis

  • Moemen Hussein1,2 na1,
  • Arnab Barua3,4 na1,
  • Mohammad Qasaimeh5,6,7,8,
  • Matthew Smardz9,10,
  • Patricia I. Diaz9,10 &
  • …
  • Haralampos Hatzikirou3,4 

npj Systems Biology and Applications , Article number:  (2026) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Ecology
  • Microbiology

Abstract

Population density plays a critical role in microbial fitness. However, its influence on pathogen colonization remains incompletely understood. Porphyromonas gingivalis (Pg) is a pathogen that plays a major role in periodontitis. It exhibits Allee-type growth and requires a quorum threshold to replicate. Yet, it is frequently detected at low abundance in vivo. We integrate quantitative growth experiments with mathematical modeling to identify ecological and stochastic determinants of Pg persistence. A cubic Allee-effect model quantifies a quorum threshold below which populations collapse. Conditioned medium from Veillonella parvula (Vp) lowers this threshold, indicating early-colonizer facilitation. Stochastic extensions and Fokker–Planck analysis show that microenvironmental noise enables persistence below the Allee barrier. This behavior is consistent with long-term subthreshold experiments that yield persistent survival. Pg–Vp co-cultures further demonstrate replicate rescue outcomes for subcritical inocula. Vp reliably reaches capacity, constraining terminal phases within the experimental horizon to coexistence or Pg extinction. A two-species replicator model maps these outcomes onto a (β, γ) plane. This mapping restricts accessible regions once Vp is established and suggests interventions that reduce facilitation and limit Pg-associated inflammation.

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Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to institutional data management policies and the use of the data in ongoing longitudinal studies regarding oral microbiome transitions, but are available from the corresponding author on reasonable request.

Code availability

All computational analyses and modeling code supporting this study are publicly available on GitHub at: https://github.com/Moemenhussein11/P.gingivalis-Colonization.

References

  1. Sun, R. et al. Changes and health inequalities in the global burden of periodontal diseases from 1990 to 2021: A population-based study. Clin. Oral. Investig. 29, 447 (2025).

    Google Scholar 

  2. Fine, D. H. & Schreiner, H. Oral microbial interactions from an ecological perspective: a narrative review. Front. Oral Health 4, https://pubmed.ncbi.nlm.nih.gov/37771470/ (2023).

  3. Genco, R. J. & Sanz, M. Clinical and public health implications of periodontal and systemic diseases: An overview. Periodontology 2000 83, 7–13 (2020).

    Google Scholar 

  4. Hajishengallis, G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat. Rev. Immunol. 15, 30–44 (2015).

  5. Nadell, C. D., Drescher, K. & Foster, K. R. Spatial structure, cooperation and competition in biofilms. Nat. Rev. Microbiol. 14, 589–600 (2016).

    Google Scholar 

  6. Baker, J. L., Mark Welch, J. L., Kauffman, K. M., McLean, J. S. & He, X. The oral microbiome: diversity, biogeography and human health. Nat. Rev. Microbiol. 22, 89–104 (2024).

    Google Scholar 

  7. Van Dyke, T. E., Bartold, P. M. & Reynolds, E. C. The nexus between periodontal inflammation and dysbiosis. Front. Immunol. 11, https://pubmed.ncbi.nlm.nih.gov/32296429/ (2020).

  8. Hooks, K. B. & O’Malley, M. A. Dysbiosis and its discontents. mBio 8, e01492–17 (2017).

    Google Scholar 

  9. Hajishengallis, G. & Lamont, R. J. Polymicrobial communities in periodontal disease: their quasi-organismal nature and dialogue with the host. Periodontology 2000 86, 210 (2021).

    Google Scholar 

  10. Hajishengallis, G. et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe 10, 497–506 (2011).

    Google Scholar 

  11. Hajishengallis, G. & Chavakis, T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat. Rev. Immunol. 21, 426–440 (2021).

  12. Lamont, R. J. & Kuboniwa, M. The polymicrobial pathogenicity of Porphyromonas gingivalis. Front. Oral Health 5, https://pubmed.ncbi.nlm.nih.gov/38736461/ (2024).

  13. Fritts, R. K., McCully, A. L. & McKinlay, J. B. Extracellular metabolism sets the table for microbial cross-feeding. Microbiol. Mol. Biol. Rev. 85, https://pubmed.ncbi.nlm.nih.gov/33441489/ (2021).

  14. Morawska, L. P., Hernandez-Valdes, J. A. & Kuipers, O. P. Diversity of bet-hedging strategies in microbial communities-Recent cases and insights. WIREs Mech. Dis. 14, https://pubmed.ncbi.nlm.nih.gov/35266649/ (2022).

  15. Hoare, A. et al. A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen. ISME J. 15, 1490–1504 (2021).

  16. Muir, E. J., Lajeunesse, M. J. & Kramer, A. M. The magnitude of Allee effects varies across Allee mechanisms, but not taxonomic groups. Oikos 2024, e10386 (2024).

    Google Scholar 

  17. Lamell, C. W., Griffen, A. L., McClellan, D. L. & Leys, E. J. Acquisition and colonization stability of Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in children. J. Clin. Microbiol. 38, 1196 (2000).

    Google Scholar 

  18. Griffen, A. L., Becker, M. R., Lyons, S. R., Moeschberger, M. L. & Leys, E. J. Prevalence of Porphyromonas gingivalis and Periodontal Health Status. J. Clin. Microbiol. 36, 3239 (1998).

    Google Scholar 

  19. Ehmke, B., Moter, A., Beikler, T., Milian, E. & Flemmig, T. F. Adjunctive antimicrobial therapy of periodontitis: long-term effects on disease progression and oral colonization. J. Periodontol. 76, 749–759 (2005).

    Google Scholar 

  20. Fujise, O., Miura, M., Hamachi, T. & Maeda, K. Risk of Porphyromonas gingivalis recolonization during the early period of periodontal maintenance in initially severe periodontitis sites. J. Periodontol. 77, 1333–1339 (2006).

    Google Scholar 

  21. Mombelli, A. Microbial colonization of the periodontal pocket and its significance for periodontal therapy. Periodontology 2000 76, 85–96 (2018).

    Google Scholar 

  22. Markowska, K., Szymanek-Majchrzak, K., Pituch, H. & Majewska, A. Understanding quorum-sensing and biofilm forming in anaerobic bacterial communities. Int. J. Mol. Sci. 25, https://pubmed.ncbi.nlm.nih.gov/39684519/ (2024).

  23. Zhou, P., Manoil, D., Belibasakis, G. N. & Kotsakis, G. A. Veillonellae: beyond bridging species in oral biofilm ecology. Front. Oral Health 2, https://pubmed.ncbi.nlm.nih.gov/35048073/ (2021).

  24. Periasamy, S. & Kolenbrander, P. E. Central role of the early colonizer Veillonella sp. in establishing multispecies biofilm communities with initial, middle, and late colonizers of enamel. J. Bacteriol. 192, 2965–2972 (2010).

    Google Scholar 

  25. Periasamy, S. & Kolenbrander, P. E. Mutualistic biofilm communities develop with Porphyromonas gingivalis and initial, early, and late colonizers of enamel. J. Bacteriol. 191, 6804 (2009).

    Google Scholar 

  26. Urbaniec, J., Xu, Y., Hu, Y., Hingley-Wilson, S. & McFadden, J. Phenotypic heterogeneity in persisters: a novel ‘hunker’ theory of persistence. FEMS Microbiol. Rev. 46, fuab042 (2021).

    Google Scholar 

  27. Allen, B. & Nowak, M. A. Cooperation and the fate of microbial societies. PLoS Biol. 11, e1001549 (2013).

    Google Scholar 

  28. Zomorrodi, A. R. & Segrè, D. Genome-driven evolutionary game theory helps understand the rise of metabolic interdependencies in microbial communities. Nat. Commun. https://pubmed.ncbi.nlm.nih.gov/29146901/ (2017).

  29. Sun, G. Q. Mathematical modeling of population dynamics with Allee effect. Nonlinear Dyn. 85, 1–12 (2016).

  30. Storn, R. & Price, K. Differential evolution—a simple and efficient heuristic for global optimization over continuous spaces. J. Glob. Optim. 11, 341–359 (1997).

    Google Scholar 

  31. Lamont, R. J. & Jenkinson, H. F. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol. Mol. Biol. Rev. 62, 1244–1263 (1998).

    Google Scholar 

  32. Mukherjee, S. & Bassler, B. L. Bacterial quorum sensing in complex and dynamically changing environments. Nat. Rev. Microbiol. 17, 371–382 (2019).

    Google Scholar 

  33. Hoek, T. A. et al. Resource availability modulates the cooperative and competitive nature of a microbial cross-feeding mutualism. PLoS Biol. 14, 1–17 (2016).

    Google Scholar 

  34. García-Ojalvo, J. & Sancho, J. M. Noise in Spatially Extended Systems. Institute for Nonlinear Science. http://link.springer.com/10.1007/978-1-4612-1536-3 (Springer New York, 1999).

  35. Méndez, V., Llopis, I., Campos, D. & Horsthemke, W. Effect of environmental fluctuations on invasion fronts. J. Theor. Biol. 281, 31–38 (2011).

    Google Scholar 

  36. Naito, M. et al. Determination of the genome sequence of Porphyromonas gingivalis strain ATCC 33277 and genomic comparison with strain W83 revealed extensive genome rearrangements in P. gingivalis. DNA Res. 15, 215–225 (2008).

    Google Scholar 

  37. Reichert-Schwillinsky, F., Pin, C., Dzieciol, M., Wagner, M. & Hein, I. Stress- and growth rate-related differences between plate count and real-time PCR data during growth of Listeria monocytogenes. Appl. Environ. Microbiol. 75, 2132–2138 (2009).

    Google Scholar 

  38. Taylor, P. D. & Jonker, L. B. Evolutionarily stable strategies with two types of players. Math. Biosci. 40, 145–156 (1978).

    Google Scholar 

  39. Cressman, R. & Tao, Y. The replicator equation and other game dynamics. Proc. Natl. Acad. Sci. 111, 10810–10817 (2014).

    Google Scholar 

  40. Abdulkareem, A. A. et al. Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis. J. Oral Microbiol. 15, https://pubmed.ncbi.nlm.nih.gov/37025387/ (2023).

  41. Abisado, R. G., Benomar, S., Klaus, J. R., Dandekar, A. A. & Chandler, J. R. Bacterial quorum sensing and microbial community interactions. mBio. 9, https://pubmed.ncbi.nlm.nih.gov/29789364/ (2018).

  42. Ammann, T. W., Belibasakis, G. N. & Thurnheer, T. Impact of early colonizers on in vitro subgingival biofilm formation. PLoS ONE 8, https://pubmed.ncbi.nlm.nih.gov/24340084/ (2013).

  43. Dennis, B. Allee effects in stochastic populations. Oikos 96, 389–401 (2002).

    Google Scholar 

  44. Dennis, B., Assas, L., Elaydi, S., Kwessi, E. & Livadiotis, G. Allee effects and resilience in stochastic populations. Theor. Ecol. 9, 323–335 (2016).

    Google Scholar 

  45. Gong, A., Walker, E. J. & Gilbert, B. Allee effects, colonization, and extinction: the surprising benefits of demographic stochasticity. Am. Nat. 206, 31–43 (2025).

    Google Scholar 

  46. Balaban, N. Q., Merrin, J., Chait, R., Kowalik, L. & Leibler, S. Bacterial persistence as a phenotypic switch. Science 305, 1622–1625 (2004).

    Google Scholar 

  47. Madianos, P. N., Papapanou, P. N., Nannmark, U., Dahlén, G. & Sandros, J. Porphyromonas gingivalis FDC381 multiplies and persists within human oral epithelial cells in vitro. Infect. Immun. 64, 660–664 (1996).

    Google Scholar 

  48. Lee, K., Roberts, J. S., Choi, C. H., Atanasova, K. R. & Yilmaz, Ö. Porphyromonas gingivalis traffics into endoplasmic reticulum-rich-autophagosomes for successful survival in human gingival epithelial cells. Virulence 9, 845–859 (2018).

  49. Li, P. et al. Controlled cellular redox, repressive hemin utilization and adaptive stress responses are crucial to metronidazole tolerance of Porphyromonas gingivalis persisters. J. Clin. Periodontol. 45, 1211–1221 (2018).

    Google Scholar 

  50. Wang, C., Li, X., Cheng, T., Sun, H. & Jin, L. Eradication of Porphyromonas gingivalis Persisters Through Colloidal Bismuth Subcitrate Synergistically Combined With Metronidazole. Front. Microbiol. 12, https://pubmed.ncbi.nlm.nih.gov/34745052/ (2021).

  51. Wang, C., Cheng, T., Li, X. & Jin, L. Metronidazole-treated Porphyromonas gingivalis persisters invade human gingival epithelial cells and perturb innate responses. Antimicrob. Agents Chemother. 64, https://pubmed.ncbi.nlm.nih.gov/32205352/ (2020).

  52. Hatzikirou, H. Statistical mechanics of cell decision-making: the cell migration force distribution. J. Mech. Behav. Mater. 27, 20180001 (2018).

    Google Scholar 

  53. Barua, A., Nava-Sedeño, J. M., Meyer-Hermann, M. & Hatzikirou, H. A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms. Sci. Rep. 10, 22371 (2020).

    Google Scholar 

  54. Barua, A. et al. Entropy-driven cell decision-making predicts ‘fluid-to-solid’ transition in multicellular systems. N. J. Phys. 22, 123034 (2020).

    Google Scholar 

  55. Pujar, A. A. et al. Microenvironmental entropy dynamics analysis reveals novel insights into Notch-Delta-Jagged decision-making mechanism. iScience 27, 110569 (2024).

    Google Scholar 

  56. Barua, A. & Hatzikirou, H. Cell decision making through the lens of Bayesian learning. Entropy 25, 609 (2023).

    Google Scholar 

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Acknowledgements

H. H. was supported by the RIG-2023-051 Khalifa University grant. P.I.D. acknowledges support from the National Institutes of Health, National Institute of Dental and Craniofacial Research (grant R21DE034093). H.H., M.Q., and P.I.D. acknowledge support from the UAE-NIH Collaborative Research grant AJF-NIH-25-KU. H.H. and A.B. acknowledge support from Volkswagenstiftung under the “Life?” program (grant 96732). M.H. acknowledges support from the Khalifa University PhD Program.

Author information

Author notes
  1. These authors contributed equally: Moemen Hussein, Arnab Barua.

Authors and Affiliations

  1. Department of Biomedical Engineering and Biotechnology, Khalifa University, Abu Dhabi, UAE

    Moemen Hussein

  2. Faculty of Engineering, Department of Mathematical Engineering and Physics, Alexandria University, Alexandria, Egypt

    Moemen Hussein

  3. Mathematics Department, Khalifa University, Abu Dhabi, UAE

    Arnab Barua & Haralampos Hatzikirou

  4. Center for Information Services and High Performance Computing, Technische Universität Dresden, Dresden, Germany

    Arnab Barua & Haralampos Hatzikirou

  5. Division of Engineering, New York University Abu Dhabi, Abu Dhabi, UAE

    Mohammad Qasaimeh

  6. Department of Mechanical and Aerospace Engineering, New York University, Brooklyn, NY, USA

    Mohammad Qasaimeh

  7. Department of Biomedical Engineering, New York University, Brooklyn, NY, USA

    Mohammad Qasaimeh

  8. Research Center for Translational Medical Devices, New York University Abu Dhabi, Abu Dhabi, UAE

    Mohammad Qasaimeh

  9. UB Microbiome Center, University at Buffalo, Buffalo, NY, USA

    Matthew Smardz & Patricia I. Diaz

  10. Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA

    Matthew Smardz & Patricia I. Diaz

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Contributions

Conceptualization: H.H.; Methodology: M.H., A.B., and H.H.; Experiments: M.S., and P.I.D. Investigation: M.H. and A.B.; Formal analysis: A.B., and M.H.; Writing—review and editing: M.H., A.B., M.Q., M.S., P.I.D., and H.H.; Supervision: H.H.; Funding acquisition: H.H., M.Q., and P.I.D.

Corresponding author

Correspondence to Haralampos Hatzikirou.

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Hussein, M., Barua, A., Qasaimeh, M. et al. Ecological and stochastic determinants of the growth and persistence of the oral pathogen Porphyromonas gingivalis. npj Syst Biol Appl (2026). https://doi.org/10.1038/s41540-026-00662-x

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  • Received: 09 November 2025

  • Accepted: 31 January 2026

  • Published: 26 February 2026

  • DOI: https://doi.org/10.1038/s41540-026-00662-x

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