Porphyromonas gingivalis

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Porphyromonas gingivalis
Systematics
Department : Bacteroidetes
Class : Bacteroidia
Order : Bacteroidales
Family : Porphyromonadaceae
Genre : Porphyromonas
Type : Porphyromonas gingivalis
Scientific name
Porphyromonas gingivalis
( Coykendall et al. 1980) Shah & Collins 1988

Porphyromonas gingivalis (P. g .; former name: Bacteroides gingivalis ) is the marker germ for severe and aggressive forms of periodontitis and thus responsible for the loss of teeth . It occurs almost exclusively in deep periodontal pockets, but also in the upper digestive tract , in the respiratory tract and in the colon . It could also beisolatedfrom the vagina in bacterial vaginosis . Its involvement in cardiovascular and other systemic diseases is also discussed. Together with Tannerella forsythia and Treponema denticola, thegerm belongsto the so-called “red complex”, the occurrence of which is almost always associated with considerable inflammation , considerable pocket depths , bleeding andloss of attachment , a destruction of the periodontium . Porphyromonas gingivalis is a short, immobile, gram-negative , anaerobic bacillus from the family Porphyromonadaceae . On blood agar is Porphyromonas gingivalis small brown to black colonies.

Porphyromonas gingivalis was found in a study from 2019 in Alzheimer's patients in the brain. The bacterium is therefore discussed as a possible cause of Alzheimer's disease.

Genome analysis

The complete 2,343,479 bp genome sequence of the bacterium was decoded in 2003. Genomic analysis of strain W83 reveals a number of virulence determinants that include at least six putative hemagglutinin-like genes and 36 previously unidentified peptidases . Genomic analysis also shows that Porphyromonas gingivalis metabolizes a number of amino acids and can produce a number of metabolic end products that are toxic to the human host and human gum tissue, respectively, which has confirmed that it is involved in the development of periodontal disease.

Virulence factors

The most important virulence factors of Porphyromonas gingivalis include gingipaine , the capsular polysaccharide and pili (fimbriae).

Gingipain

Gingipaines are proteases that are secreted by Porphyromonas gingivalis , specifically Arg-Gingipain (Gingipain-R, RGP) and Lys-Gingipain (Gingipain-K, KGP). Among other functions, they break down cytokines , which downregulates the host response in the form of reduced inflammation.

Capsular polysaccharide

The encapsulated strain of Porphyromonas gingivalis is more virulent than the unencapsulated strain. The capsule is a capsular polysaccharide and regulates cytokine production , particularly the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNF-α, which indicate an evasive reaction by the host.

Fimbriae

The fimbriae are involved in adhesion, invasion and colonization. Porphyromonas gingivalis has the following types of fimbria:

Long fimbriae

Long fimbriae (FimA) ensure adhesion of the pathogen and the build-up of biofilms . They act as adhesins , especially of the antigen I / II protein family, which support the invasion of the host cells and contribute to the pathogenicity of Porphyromonas gingivalis .

Short fimbriae

Short fimbriae (Mfa1) are responsible for the formation of microcolonies through autoaggregation and ensure the linkage with other types of bacteria. Together with Streptococcus gordonii (especially SspB streptococci) they form a biofilm through interaction with the SspB streptococcal surface polypeptide . This interaction may play a key role in the invasion of the dentinal tubules .

Accessory fimbriae

The accessory fimbriae (Fim C, D, and E) associate with the long fimbriae and play a role in binding to host matrix proteins and interacting with the CXC chemokine receptor 4 (CXCR4). Experiments have shown that the loss of the accessory fimbriae significantly weakens the virulence of the pathogen.

Spread in the tissue

It has been shown that Porphyromonas gingivalis can penetrate intracellularly into macrophages , epithelial , endothelial and smooth muscle cells , survive there and spread from one cell to the next. Porphyromonas gingivalis could therefore possibly use these cells as a means of transport to get to peripheral tissues. Porphyromonas gingivalis , for example , could be detected in atherosclerotic plaques (deposits on the blood vessel walls, colloquially "hardening of the arteries"), which can contribute to the progression of atherosclerosis.

A possible cause of Alzheimer's disease

In 2019, a study caused a sensation in which the authors were able to detect both Porphyromonas gingivalis and its metabolic products, gingipaine, in the brains of Alzheimer's patients. In the laboratory, the authors were able to show in vitro and in vivo that gingipaines have the ability to influence the structure of tau proteins . In mice, an orally applied protease inhibitor (COR388) was able to stop the multiplication of the pathogens and the progressive neurodegeneration. The COR388 inhibitor had been in a phase I clinical study with healthy volunteers since December 2017 . Another, randomized, placebo- controlled, double-blind phase I study with Alzheimer's patients began in February 2018. Both studies were successfully completed and a larger phase II / III study started in March 2019.

therapy

As part of a treatment of periodontitis which are root surfaces of the teeth by means of debridement mechanically cleaned. If there is evidence of an increased concentration of Porphyromonas gingivalis and significant signs of inflammation , antibiotics are also administered orally. Porphyromonas gingivalis is sensitive to metronidazole , clindamycin and doxycycline .

Web links

Individual evidence

  1. Philip Marsh, Michael V. Martin: Orale Mikrobiologie: 60 tables . Georg Thieme Verlag, 2003, ISBN 978-3-13-129731-0 , p. 33.
  2. RT Demmer, M. Desvarieux: Periodontal infections and cardiovascular disease: the heart of the matter. In: Journal of the American Dental Association. Volume 137 Suppl, October 2006, pp. 14S-20S, PMID 17012731 (review).
  3. M. Hussain, CM Stover, A. Dupont: P. gingivalis in Periodontal Disease and Atherosclerosis - Scenes of Action for Antimicrobial Peptides and Complement. In: Frontiers in immunology. Volume 6, 2015, p. 45, doi: 10.3389 / fimmu.2015.00045 , PMID 25713575 , PMC 4322733 (free full text) (review).
  4. Naito M, Hirakawa H, Yamashita A, 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 . In: DNA Res . 15, No. 4, August 2008, pp. 215-25. doi : 10.1093 / dnares / dsn013 . PMID 18524787 . PMC 2575886 (free full text).
  5. a b Stephen S. Dominy, Casey Lynch et al. a .: Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors. In: Science Advances. 5, 2019, p. Eaau3333, doi : 10.1126 / sciadv.aau3333 .
  6. a b Joachim Czichos: Bacterial infection as a cause of Alzheimer's dementia. In: Wissenschaft-aktuell.de. January 24, 2019, accessed January 26, 2019 .
  7. L. Lin, C. Li et al. a .: Virulence genes of Porphyromonas gingivalis W83 in chronic periodontitis. In: Acta odontologica Scandinavica. Volume 67, number 5, 2009, pp. 258-264, doi : 10.1080 / 00016350902841890 , PMID 22443638 .
  8. KE Nelson, RD Fleischmann u. a .: Complete Genome Sequence of the Oral Pathogenic Bacterium Porphyromonas gingivalis Strain W83. In: Journal of Bacteriology. 185, 2003, p. 5591, doi: 10.1128 / JB.185.18.5591-5601.2003 .
  9. PG Stathopoulou, MR Benakanakere u. a .: Epithelial cell pro-inflammatory cytokine response differs across dental plaque bacterial species. In: Journal of clinical periodontology. Volume 37, number 1, January 2010, pp. 24-29, doi : 10.1111 / j.1600-051X.2009.01505.x , PMID 20096064 , PMC 2900159 (free full text).
  10. A. Singh, T. Wyant et al. a .: The capsule of Porphyromonas gingivalis leads to a reduction in the host inflammatory response, evasion of phagocytosis, and increase in virulence. In: Infection and Immunity. Volume 79, number 11, November 2011, pp. 4533-4542, doi : 10.1128 / IAI.05016-11 , PMID 21911459 , PMC 3257911 (free full text).
  11. M. Kuboniwa, Y. Hasegawa et al. a .: P. gingivalis accelerates gingival epithelial cell progression through the cell cycle. In: Microbes and infection. Volume 10, number 2, February 2008, pp. 122–128, doi: 10.1016 / j.micinf.2007.10.011 , PMID 18280195 , PMC 2311419 (free full text).
  12. X. Lin, J. Wu, H. Xie: Porphyromonas gingivalis minor fimbriae are required for cell-cell interactions. In: Infection and Immunity. Volume 74, number 10, October 2006, pp. 6011-6015, doi: 10.1128 / IAI.00797-06 , PMID 16988281 , PMC 1594877 (free full text).
  13. DL Pierce, S. Nishiyama et al. a .: Host adhesive activities and virulence of novel fimbrial proteins of Porphyromonas gingivalis. In: Infection and Immunity. Volume 77, number 8, August 2009, pp. 3294-3301, doi: 10.1128 / IAI.00262-09 , PMID 19506009 , PMC 2715668 (free full text).
  14. EV Kozarov: Human Atherosclerotic Plaque Contains Viable Invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 25, 2005, p. E17, doi: 10.1161 / 01.ATV.0000155018.67835.1a .
  15. Irina M. Velsko, Sasanka S. Chukkapalli u. a .: Active Invasion of Oral and Aortic Tissues by Porphyromonas gingivalis in Mice Causally Links Periodontitis and Atherosclerosis. In: PLoS ONE. 9, 2014, p. E97811, doi: 10.1371 / journal.pone.0097811 .
  16. Zahra Armingohar, Jørgen J. Jørgensen u. a .: Bacteria and bacterial DNA in atherosclerotic plaque and aneurysmal wall biopsies from patients with and without periodontitis. In: Journal of Oral Microbiology. 6, 2014, p. 23408, doi: 10.3402 / jom.v6.23408
  17. Clinical study (phase I): Study of COR388 HCl in Healthy Subjects at Clinicaltrials.gov of the NIH
  18. Clinical Study (Phase I): A Multiple Ascending Dose Study of COR388 at Clinicaltrials.gov of the NIH
  19. Clinical study (Phase II / III): GAIN Trial: Phase 2/3 Study of COR388 in Subjects With Alzheimer's Disease at Clinicaltrials.gov of the NIH
  20. ^ Adjuvant antibiotics in periodontal therapy , joint statement of the German Society for Tooth, Oral and Jaw Diseases (DGZMK) and the German Society for Periodontology (DGP) (2003). Retrieved October 23, 2017.
  21. Peter Kolling, Gerwalt Muhle: Compromises and Limits in Periodontology . Spitta Verlag GmbH & Co. KG, 2003, ISBN 978-3-934211-62-9 , p. 135.