Микрофлора и бактериальные ловушки в патогенезе пародонтита

   Основным этиологическим фактором возникновения и прогрессирования пародонтита является биоплёнка – организованное скопление микроорганизмов в сложном межклеточном матриксе. Мультивидовые биоплёнки демонстрируют сложные коммуникации между бактериями и поддерживают симбиотические связи – чувства кворума (QS-quorum sensing) в микробиоме [1].

   Ключевыми посредниками коммуникации бактерий между собой или клетками организма-хозяина, считаются бактериальные внеклеточные везикулы (ВEV – Bacterial Extracellular Vesicles) [2, 3].

   Бактериальные везикулы обеспечивают селективное преимущество родительским клеткам, способствуют образованию биоплёнок, расширению границ, участвуют в транспорте вирулентных факторов, переносе генетической информации между клетками, могут распространяться на большие расстояния и играть ключевую роль в развитии болезней. В этом обзоре была проанализирована роль BEV в коммуникации между бактериями и клетками организма-хозяина, рассмотрены ключевые механизмы воспаления и иммунной резистентности.

1. Abdulkareem A.A., Al-Taweel F.B., Al-Sharqi A.J.B., Gul S.S., Sha A., et al. Current concepts in the pathogenesis of periodontitis: from symbiosis to dysbiosis. J Oral Microbiol. 2023 Apr. 2. 15 (1). 2197779. doi: 10.1080/20002297.2023.2197779.

2. Zhang R., Li G., Wu Y., Wang X., Luan Q. Pathogenic mechanisms and potential applications of extracellular vesicles from periodontal pathogens in periodontitis. Front Immunol. 2024 Dec. 20. 15. 1513983. doi: 10.3389/fimmu.2024.1513983.

3. Zou C., Zhang Y., Liu H., Wu Y., Zhou X. Extracellular vesicles: recent insights into the interaction between host and pathogenic bacteria. Front Immunol. 2022. May 25. 13. 840550. doi: 10.3389/fimmu.2022.840550.

4. Сабирова A.И., Aкрамов И.A., Рамазанова З.Д., Сергеева B.B., Ибишева Л.К. Современные аспекты эпидемиологических вопросов заболеваний тканей пародонта. The Scientific Heritage. 2021. 73 (2). 31–38. doi: 10.24412/9215-0365-2021-73-2-31-38.

5. Jakubovics N.S., Goodman S.D., Mashburn‐warren L., et al. The dental plaque biofilm matrix. Periodontol 2000. 2021 Jun. 86 (1). 32–56. doi: 10.1111/prd.12361.

6. Nie X., Li Q., Chen X., Onyango S., Xie J., et al. Bacterial extracellular vesicles: Vital contributors to physiology from bacteria to host. Microbiol Res. 2024. Jul. 284. 127733. doi: 10.1016/j.micres.2024.127733.

7. Zhao X., Wei Y., Bu Y., Ren X., Dong Z. Review on bacterial outer membrane vesicles: structure, vesicle formation, separation and biotechnological applications. Microb Cell Fact. 2025 Jan. 21. 24 (1). 27. doi: 10.1186/s12934-025-02653-9.

8. Bittel M., Reichert P., Sarfati I., Dressel A., Leikam S., et al. Visualizing transfer of microbial biomolecules by outer membrane vesicles in microbe-host-communication in vivo. / J Extracell Vesicles. 2021 Oct. 10 (12). e12159. doi: 10.1002/jev2.12159.

9. Avila-Calderón E.D., Ruiz-Palma M.D.S., Aguilera-Arreola M.G., Velázquez-Guadarrama N., Ruiz E.A., Gomez-Lunar Z., et al. Outer membrane vesicles of gram-negative bacteria: an outlook on biogenesis. Front Microbiol. 2021 Mar. 4 (12). 557902. doi: 10.3389/fmicb.2021.557902.

10. Xie J., Haesebrouck F., Van Hoecke L., Vandenbroucke R. Bacterial extracellular vesicles: an emerging avenue to tackle diseases. Trends Microbiol. 2023. 31. 1206–24. doi:10.1016/j.tim.2023.05.010).

11. Gan Y., Zhao G., Wang Z., Zhang X., Wu M., et al. Bacterial membrane vesicles: physiological roles, infection immunology, and applications. Advanced Sci (Weinheim Baden-Wurttemberg Germany). 2023 Sep. 10 (25). e2301357. doi: 10.1002/advs.202301357.

12. Xie J., Li Q., Haesebrouck F., Van Hoecke L., Vandenbroucke R.E. The tremendous biomedical potential of bacterial extracellular vesicles. Trends Biotechnol. 2022. 40. 1173–94. doi: 10.1016/j.tibtech.2022.03.005

13. Toyofuku M., Schild S., Kaparakis-Liaskos M., Eberl L.. Composition and functions of bacterial membrane vesicles. Nat Rev Microbiol. 2023. 21. 415–30. doi: 10.1038/s41579-023-00875-5

14. Jennings M.P., Day C.J., Atack J.M. How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach. Microbiology (Reading). 2022 Mar. 168 (3). 001157. doi: 10.1099/mic.0.001157.

15. Jiang M., Wang Z., Xia F., Wen Z., Chen R., et al. Reductions in bacterial viability stimulate the production of extra-intestinal pathogenic escherichia coli (Expec) cytoplasm-carrying extracellular vesicles (Evs). PloS Pathog. 2022 Oct. 19. 18 (10). e1010908. doi: 10.1371/journal.ppat.1010908.

16. Zhang Z., Liu S., Zhang S., Li Y., Shi X., et al. Porphyromonas gingivalis outer membrane vesicles inhibit the invasion of Fusobacterium nucleatum into oral epithelial cells by downregulating fada and foma. J Periodontol. 2022. 93. 515–25. doi: 10.1002/jper.21-0144).

17. Chen G., Sun Q., Cai Q., Zhou H. Outer Membrane Vesicles From Fusobacterium nucleatum Switch M0-Like Macrophages Toward the M1 Phenotype to Destroy Periodontal Tissues in Mice. Front Microbiol. 2022 Mar. 21 (13). 815638. doi: 10.3389/fmicb.2022.815638.

18. Settem R.P., Ruscitto A., Chinthamani S., Honma K., Sharma A. Tannerella forsythia scavenges Fusobacterium nucleatum secreted NOD2 stimulatory molecules to dampen oral epithelial cell inflammatory response. Mol Oral Microbiol. 2024. 39 (2). 40–46. doi: 10.1111/omi.12429.

19. Sumaya A.S.M. Al-Hamdoni., Amera Al-Rawi Effect of Lubanum and Potash Alum on Co-aggregation and Biofilm Formation of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia. Rafidain Journal of Science. March 2023. 17. 32 (1). 45–52. doi: 10.33899/rjs.2023.177287.

20. Faddetta T., Vassallo A., Del Duca S., Gallo G., Fani R., et al. Unravelling the DNA sequences carried by streptomyces coelicolor membrane vesicles. Sci Rep. 2022. Oct 5. 12 (1). 16651. doi: 10.1038/s41598-022-21002-z.

21. Schäffer C., Andrukhov O. The intriguing strategies of Tannerella forsythia's host interaction. Front Oral Health. 2024 May 30. 5. 1434217. doi: 10.3389/froh.2024.1434217.

22. Xu W., Zhou W., Wang H., et al. Roles of Porphyromonas gingivalis and its virulence factors in periodontitis. Adv Protein Chem Struct Biol. 2020. 120. 45–84. doi: 10.1016/bs.apcsb.2019.12.001.

23. Frey A.M., Satur M.J., Phansopa C., Honma K., Urbanowicz P.A., et al. Characterization of Porphyromonas gingivalis sialidase and disruption of its role in host-pathogen interactions. Microbiology. (2019) 165 (11): 1181–97. doi: 10.1099/mic.0.000851.

24. Kendlbacher F.L., Bloch S., Hager-Mair F.F., Bacher J., Janesch B., Multispecies biofilm behavior and host interaction support the association of Tannerella serpentiformis with periodontal health. Mol Oral Microbiol. 2023 Apr. 38 (2). 115-133. doi: 10.1111/omi.12385.

25. Grenier D. Porphyromonasт gingivalis outer membrane vesicles mediate coaggregation and piggybacking of Тreponema denticola and Lachnoanaerobaculum saburreum. Int J Dent. 2013 Jan. 13. 2013. 305476. doi: 10.1155/2013/305476.

26. Kim H.Y., Song M.K., Gho Y.S., Kim H.H., Choi B.K. Extracellular vesicles derived from the periodontal pathogen Filifactor alocis induce systemic bone loss through Toll-like receptor 2. J Extracell Vesicles. 2021 Oct. 10 (12). e12157. doi: 10.1002/jev2.12157.

27. Song M.K., Kim H.Y., Choi B.K., Kim H.H. Filifactor alocis-derived extracellular vesicles inhibit osteogenesis through tlr2 signaling. Mol Oral Microbiol. 2020. 35. 202–10. doi: 10.1111/omi.12307.

28. Kim H.Y., Lim Y., An S.J., Choi B.K. Characterization and immunostimulatory activity of extracellular vesicles from Filifactor alocis. Mol Oral Microbiol. 2020 Jan. 35 (1). 1–9. doi: 10.1111/omi.12272.

29. Wang J., Liu C., Cutler J., Ivanovski S., Lee R.S., et al. Microbial- and host immune cell-derived extracellular vesicles in the pathogenesis and therapy of periodontitis : A narrative review. J Periodontal Res. 2024. 59 (6). 1115–29. doi: 10.1111/jre.13283.

30. Fan R., Zhou Y., Chen X., Zhong X., He F., et al. Porphyromonas gingivalis outer membrane vesicles promote apoptosis via msrna-regulated DNA methylation in periodontitis. Microbiol Spectr. 2023 Feb. 14. 11 (1). e0328822. doi: 10.1128/spectrum.03288-22.

31. Cai R., Wang L., Zhang W., Liu B., Wu Y., et al. The role of extracellular vesicles in periodontitis: pathogenesis, diagnosis, and therapy. Front Immunol. 2023 Apr. 11 (14). 1151322. doi: 10.3389/fimmu.2023.11513.

32. Doré E., Boilard E. Bacterial extracellular vesicles and their interplay with the immune system. Pharmacol Ther. 2023 Jul. 247. 108443. doi: 10.1016/j.pharmthera.2023.108443.

33. Buonavoglia A. et al. Antibiotics or no antibiotics, that is the question: An update on efficient and effective use of antibiotics in dental practice. Antibiotics (Basel). 2021 May 9. 10 (5). 550. doi: 10.3390/antibiotics10050550.

34. Abdulkareem А.A., Abdulbaqi H.R, Gul S., Milward M., Chasib N., et al. Classic vs. novel antibacterial approaches for eradicating dental biofilm as adjunct to periodontal debridement : an evidence-based overview. Antibiotics. 2021. 11 (1). 9. doi: 10.3390/antibiotics11010009.

35. Ho M.Y., Liu S., Xing B. Bacteria extracellular vesicle as nanopharmaceuticals for versatile biomedical potential / Nano Converg. 2024 Jul. 11. 11 (1). 28. doi: 10.1186/s40580-024-00434-5.

36. Radu C.M., Radu C.C., Arbănaşi E.M., Hogea T., Murvai V.R., et al. Exploring the Efficacy of Novel Therapeutic Strategies for Periodontitis : A Literature Review. Life (Basel). 2024 Apr. 3. 14 (4). 468. doi: 10.3390/life14040468.