The Role of Gingipains in the Pathogenicity of Porphyromonas Gingivalis

Porphyromonas gingivalis obtains iron using specific outer membrane receptors, proteases known as gingipains and lipoproteins. The bacterium is also capable of evading the host immune response without inflammatory response suppression. Actually, P. gingivalis and other pathogenic bacteria may take advantage of inflammation -deriving nutrients and iron from the inflammatory exudate.¹ Twenty-two strains of P. gingivalis with varying degrees of invasiveness and virulence have been identified.²

Ongoing research into the underlying mechanisms of P. gingivalis’ pathogenicity focuses on gingipains — cysteine proteinases anchored to its cell surface.³ Gingipains work by splitting the protein genetic sequences from lysine or arginine residues: lysine-gingipain, arginine-gingipain A, and arginine-gingipain B.^4–6  These principal gingipains of P. gingivalis are either released into the milieu or become attached to other cell surfaces.^3,7

 As virulence factors, their role in periodontal tissue degradation and the breakdown of iron-binding proteins is to attack critical components of the extracellular matrix, disrupting the epithelium’s barrier function and allowing P. gingivalis to enter subepithelial tissues.³

Gingipains can also enmesh the circulating proteins necessary for binding apoptotic and necrotic cells and cellular DNA to clean up after injury. These gingipains-proteins interactions interrupt the host’s immunological response, allowing P. gingivalis to remain in the host longer.

P. gingivalis can delay the recruitment of neutrophils — an essential step in immune response and a feature in healthy periodontium, which permits the bacterial community time to colonize.^5,8Moreover, by activating and exploiting the C5a-receptor signaling, P. gingivalis can block the complement cascade as well as undermine the leukocyte killing capacity.^7–9

References

1. Mysak J, Podzimek S, Sommerova P, et al. Porphyromonas gingivalis: major periodontopathic pathogen overview. J Immunol Res. 2014;2014:e476068.
2. Igboin CO, Griffen AL, Leys EJ. Porphyromonas gingivalis strain diversity. J Clin Microbiol. 2009;47:3073–3081.
3. Lunar Silva I, Cascales E. Molecular strategies underlying Porphyromonas gingivalis virulence. J Mol Biol. 2021;433:166836.
4. How KY, Song KP, Chan KG. Porphyromonas gingivalis: an overview of periodontopathic pathogen below the gum line. Front Microbiol. 2016;7:53.
5. Chopra A, Bhat SG, Sivaraman K. Porphyromonas gingivalis adopts intricate and unique molecular mechanisms to survive and persist within the host: a critical update. J Oral Microbiol. 2020;12:1801090.
6. Nara PL, Sindelar D, Penn MS, Potempa J, Griffin WST. Porphyromonas gingivalis outer membrane vesicles as the major driver of and explanation for neuropathogenesis, the cholinergic hypothesis, iron dyshomeostasis, and salivary lactoferrin in Alzheimer’s disease. J Alzheimers Dis JAD. 2021;82:1417–1450.
7. Patel S, Howard D, French L. Susceptibility to gingipains and transcriptomic response to P. gingivalis highlights the ribosome, hypothalamus, and cholinergic neurons.
8. Hajishengallis G, Lamont RJ. Breaking bad: manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol. 2014;44:328–338.
9. Hajishengallis G, Liang S, Payne MA, et al. A low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and the complement pathway. Cell Host Microbe. 2011;10:497–506.

This information originally appeared in Marsh I, Matthews A. The pathogenicity of Porphyromonas gingivalis. Dimensions of Dental Hygiene. 2022;20(10)34-37.