|Year : 2015 | Volume
| Issue : 1 | Page : 51-58
Porphyromonas gingivalis : Its virulence and vaccine
Nymphea Pandit1, Radha Changela2, Deepika Bali1, Priyanka Tikoo1, Shalini Gugnani1
1 Department of Periodontology and Oral Implantology, Dayanand Anglo Vedic Centenary Dental College (D.A.V. ©Dental College), Yamuna Nagar, Haryana, India
2 Department of Periodontology and Oral Implantology, Government Dental College and Hospital, Jamnagar, Gujarat, India
|Date of Web Publication||18-Mar-2015|
Dr. Priyanka Tikoo
H.No. 2001, Sector 17, Huda, Jagadhri - 135 003, Haryana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: The microbial florae in adult periodontitis lesions are comprised of anaerobic rods with Porphyromonas gingivalis as one of the major components (Slots 1976; Slots 1979; and Tanner et al., 1979). P. gingivalis is a black-pigmented gram-negative anaerobic rod and a secondary colonizer of dental plaque requiring antecedent organisms. The presence of this organism either alone or as a mixed infection with other bacteria and with the absence of beneficial species appears to be essential for disease activity. It is a predominant member of the subgingival microbiota in disease. It possesses and "excretes" numerous potentially toxic virulence factors. Aim of this study is to perform a systematic review of studies on P. gingivalis and its virulence factors with a special focus on its vaccine. Materials and Methods: An electronic and manual search based on agreed search phrases between the primary investigator and a secondary investigator was performed for the literature review till January 2014. The articles that were identified by this systematic review (total of 190) were analyzed in detail, which included the study of inference and conclusion. Conclusions: Within the limits of this systematic review, it can be concluded that P. gingivalis induce immune inflammatory response in periodontitis subjects. Therapeutic vaccines need to be developed and studied for their efficacy in controlling periodontitis.
Keywords: Gingipains, host cells, P. gingivalis, virulence factors
|How to cite this article:|
Pandit N, Changela R, Bali D, Tikoo P, Gugnani S. Porphyromonas gingivalis : Its virulence and vaccine. J Int Clin Dent Res Organ 2015;7:51-8
|How to cite this URL:|
Pandit N, Changela R, Bali D, Tikoo P, Gugnani S. Porphyromonas gingivalis : Its virulence and vaccine. J Int Clin Dent Res Organ [serial online] 2015 [cited 2021 May 15];7:51-8. Available from: https://www.jicdro.org/text.asp?2015/7/1/51/153496
| Introduction|| |
Porphyromonas gingivalis , a black-pigmented gram-negative anaerobic rod, has been implicated as a major pathogen of chronic periodontitis. Recent studies using deoxyribonucleic acid (DNA) hybridization also indicated the increased prevalence of P. gingivalis as well as other 'red complex species' (P. gingivalis, Treponema denticola, and Tannerella forsythia) in the subjects with chronic periodontitis.  It is also evident that the colonization of the putative pathogenic bacteria in subgingival plaque is not sufficient for the initiation/onset of periodontitis as most periodontopathic bacteria including P. gingivalis may also be present at healthy sites (around 11.2 times less in healthy sites than periodontitis).  Thus, the onset and progress of chronic periodontitis is based on the balance between the pathogenesis of the periodontopathic microorganisms and the host-defense against them [Figure 1].
The complex interaction to the host response fundamentally responsible for chronic periodontitis cannot be reproduced in vitro. The studies with animal models that P. gingivalis can induce experimental periodontitis with alveolar bone losses clearly indicate that P.gingivalis is a major causative pathogen of chronic periodontitis.  Its pathogenic factors could be potentially involved solely or cooperatively in every step of the onset and progression of the disease. The virulence factors of P. gingivalis including fimbriae, hemagglutinin, capsule, lipopolysaccharide (LPS), outer membrane vesicles, organic metabolites such as butyric acid, and various enzymes such as Arg- and Lys-gingipains, collagenase, gelatinase, and hyaluronidase, could contribute to the induction of chronic periodontitis in diverse ways. 
Virulence factors are described as molecules that result in the establishment and maintenance of a species associated with or within the confines of a host.  Virulence factors are classically believed to harm the host, but they can also function in the establishment of a symbiotic or parasitic relationship between the bacterial species and the host.
Virulence factors of P. gingivalis
- Involved in colonization and attachment:
- Outer membrane proteins and vesicles
- Involved in evading (modulating) host responses:
- Ig and complement proteases, otherantiphagocytic products
- Involved in damaging host tissues and spreading:
- Proteinases (Arg- and Lys-gingipains)
- Fibrinolytic, keratinolytic, and other hydrolytic enzymes.
| Involved in Colonization and Attachment|| |
Structure and situation: Fimbriae or pili are proteinaceous, filamentous appendages that protrude outwards from the bacterial cell surface.  With only one or two exceptions, all of the P. gingivalis strains so far examined contain fimbriae arranged in a peritrichous fashion over the surface of the cell. Ultrastructural examination has revealed the presence of peritrichious fimbriae, 0.3-3.0 μm long and 5 nm wide, on most strains of P. gingivalis. 
Types: The first fimbriae are called major, long, or FimA fimbriae, and the second ones are referred to as minor, short, or Mfa1 fimbriae.  The presence of more than one type of fimbriae on P. gingivalis has recently become apparent depending upon the genotype (I-V and Ib).
Fimbriae play a crucial role in virulence by stimulating bacterial attachment to host cells or tissues. Fimbriae appear to be a major adherence-mediating determinant of P. gingivalis. Immunization with purified fimbriae confers protection against periodontal destruction in a gnotobiotic rat model  [Figure 2].
|Figure 2: Numerous thin fibrils or fimbriae (F) emerge from the surface of the cells|
Click here to view
The initial step of P. gingivalis attachment to the oral tissue is fimbriae-mediated. Ogawa et al., recently investigated the contribution of various regions of the fimbriae to binding to the human gingival fibroblast cell line.  Purified, intact, and radiolabeled fimbriae bound firmly to the surface of the fibroblasts. The synthetic peptides, when either added first to the fibroblast cells or concomitantly with the intact fimbriae, inhibited binding in a dose-dependent fashion.
In addition to mediating adherence, fimbriae have a variety of other properties (such as chemotactic properties and cytokine induction). The fimbriae werealso highly immunogenic, eliciting both an antibodyand cell-mediated response in serum and saliva. 
Structure and situation: Hemagglutinin proteins are important virulence factors for a number of bacterial species. These enzymes are either exposed at the surface (in the outer membrane) of the bacterium where they are able to come into contact with host cells and tissues or within the periplasmic space from where they are capable of being transported to the cell surface. 
Types: P. gingivalis produces at least five hemagglutinating molecules. Three hag genes encoding hemagglutinins have been cloned.
When expressed on the bacterial cell surface, hemagglutinins may promote colonization by mediating the binding of bacteria to receptors (usually oligosaccharides) on human cells. P. gingivalis binding to erythrocytes with the help of hemagglutinin may also serve a nutritional function as it utilizes heme for growth.
It is clear that basically all hemagglutinin activity is related to hemagglutinin-adhesin domains of RgpA, Kgp, and HagA.  Arecent study by Lepine et al., revealed 9-10 different restriction polymorphism profiles using hagC and hagA as probes.  These results suggest that several copies of this hemagglutinin gene are located on the chromosome of P. gingivalis.
Duncan et al., have demonstrated that the P. gingivalis hemagglutinins may also participate inthe binding of the bacterium to host cells otherthan red blood cells. 
Outer membrane proteins/vesicles
Structure and situation: They are released from the outer membrane proper during growth and are referred to as outer membrane vesicles. Trapped within these closed sacs are numerous enzymes that occur in the periplasmic region of the intact cell. These include phospholipase C, proesterases, alkaline phosphatase, hemolysins, and autolysins.  The majority of the cells' Arg-gingipain cysteine protease was localized in the outer membrane vesicles.
Vesicles are able to fuse with the outer membrane of other bacterial species, into which virulence factors are released, resulting in an impairment of target cells. Outermembrane vesicles from P. gingivalis enhance interleukin-12 induced interferon-c production by T cells, which may augment immunopathology noted in periodontitis.  This activity was also noted with the outer membrane from the microorganism, as well as with LPS.
| Involved in Evading Host Response|| |
Structure and situation: Bacterial capsules have been considered major virulence factors on the bacterial cell surface.  It is formed by a polysaccharide heteropolymer on the outer membrane of the bacterial cell (Woo et al., 1979).  Mansheim and Kasperdetermined that the capsule of P. gingivalis 381 contained galactose, glucose, and glucosamine;  whereas, Okuda et al., confirmed the presence of these sugars along with rhamnose, glucose, galactose, mannose, and methylpentose. 
Types: Six serotypes (K1-K6) and K negative isolates have been identified based on capsular K-antigens. 
The presence of a capsule in P. gingivalis has been considered an important antiphagocytic virulence factor. The highly encapsulated P. gingivalis strains exhibit decreased autoagglutination, lower buoyant densities, and are more hydrophilic than the less encapsulated strains. , Increased encapsulation is also correlated with increased resistance to phagocytosis, serum resistance, and decreased induction of polymorphonuclear leukocyte chemiluminescence. The decreased tendency for the highly encapsulated strains to be phagocytized has been proposed to be due to the increased hydrophilicity of the strains and their decreased ability to activate the alternative complement pathway.
LPS and lipid A component
Structure and situation: LPS is the major macromolecule found on the outer surface of gram-negative bacteria. LPS is typically composed of three domains: Lipid A, a short core oligosaccharide, and an O-antigen that may be a long polysaccharide. Lipid A is the innermost component of LPS. It is conserved in structure and forms the outer leaflet of the outer membrane [Figure 3].
|Figure 3: Lipopolysaccharide (LPS).a = O antigen, b = core oligosaccharide, c = lipid A|
Click here to view
LPS is critical to the bacterium for maintaining its structural integrity, and for establishing a selective permeability barrier that limits entry of hydrophobic molecules and toxic chemicals such as detergents and antibiotics.  LPS is also required for the proper folding and insertion of many outer membrane proteins [Figure 4].
Lipid A, also known as endotoxin, is the bioactive region of LPS that is recognized by the innate immune system. P. gingivalis agonist lipid A structures induced the expression of human β-defensin-1, -2, and -3, while P. gingivalis antagonist lipid A species downregulated their expression. 
| Involved in Damaging Host Tissues and Spreading|| |
Structure and situation: The Arg- and Lys-proteinases are cysteine proteinases and have been given the common name, gingipains. These enzymes are either exposed at the surface (in the outer membrane) of the bacterium where they are able to come into contact with host cells and tissues or within the periplasmic space capable of being transported to the cell surface, and in outer membrane vesicles, which are sloughed from the outer membrane during growth. 
Types: Gingipains, including arginine-specific gingipains (Arg-gingipain-A, RgpA, and Arg gingipain-B, RgpB) and lysine-specific gingipain (Lys-gingipain, Kgp), are encoded by three different genes referred to as rgpA, rgpB, and kgp [Figure 5]. 
Function of gingipains
- Adherence and colonization: The gingipains are themselves, potent non-fimbrial adhesins avidly binding several extracellular matrix proteins such as fibrinogen, fibronectin, laminin, and collagen type V.  They also apparently mediate a tight adherence to epithelial cells and gingival fibroblasts with Kgp being implicated as providing most of the binding.
- Gingipains in hemoglobin binding and heme acquisition: Gingipains exert a sequential action on which Rgps converts oxyhemoglobin to methemoglobin, which render the hemoglobin more susceptible to degradation by Kgp.  The occurrence of gingipains in large complexes is a very cleaver design to facilitate hemoglobin degradation and the capture of the released heme is accomplished with high affinity by hemagglutinin-adhesin-2. Gingipains may function as hemophore-like proteins; shuttling captured heme to a hemoglobin receptor (HmuR) in the outer membrane.
- Production of nutritious peptides: Gingipains as the most "aggressive" endopeptidases degrade serum and tissue-derived proteins. The gingipain generated protein fragments are finally subjected to the action of di- and tripeptidyl peptidases to release di- and tripeptides to be transported into the cell and used in P.gingivalis carbon and energy metabolism. 
- Degradation of antibacterial peptides: In densely populated biofilm, gingipains as well as proteases released by other periodontopathogens can proteolytically inactivate cationic antimicrobial peptides to enable the survival of other bacterial species which are highly sensitive to them.  Degradation of cationic antimicrobial peptides also inactivates cationic antimicrobial peptides' ability to neutralize LPSs, which may lead to exacerbated, sustained production of proinflammatory cytokines.
- Exploiting complement: P. gingivalis is resistant to killing by the human complement system. In a large part, this resistance is dependent on proteolytic activity of gingipains degrading different components of complement.  In addition, gingipains also contribute to proteolysis independent protection of P. gingivalis against complement-mediated lysis. This is achieved through the capture of the human complement inhibitor C4b-binding protein, thus, hindering deposition of the membrane attack complex on the P. gingivalis surface. 
- Direct degradation of extracellular matrix proteins: Gingipains efficiently degrade several extracellular matrix proteins in vitro gingipains can accomplish a lot more harm indirectly by disturbing the protease-protease inhibitor balance. In the case of human gingival fibroblasts, it was shown that matrix metalloprotease-1 expression was stimulated by Rgp activity.  Latent matrix metalloproteases can be directly activated by gingipains.
Structure and situation: Collagenase is perhaps the most important of the P. gingivalis proteolytic enzymes. These enzymes are either exposed at the surface (in the outer membrane) of the bacterium where they are able to come into contact with host cells and tissues, within the periplasmic space capable of being transported to the cell surface or in outer membrane vesicles. 
If expressed in vivo, it is a major destructive enzyme (virulence factor) associated with the soft tissue destruction characteristic of human periodontitis.  Mayrand and Grenier were able to dissect the collagenolytic activity into at least two activities: A specific collagenase activity and nonspecific proteinase activity.  These thiol-dependent collagenolytic enzymes had a molecular weight of 70 kDa and were purified from the spent culture supernatant, and their inhibition with serum components was studied.
In a study, Hoover and Felton  and Li et al.,  used specific P. gingivalis collagenase-deficient mutants generated by nitrosoguanidine mutagenesis and showed that the mutants possessed significantly decreased interaction (that is, adherence) to A. viscosus compared with its wild type parent. Takahashi et al., were able to isolate a prtCgene from P. gingivalis strain 53977, which expressed collagenase activity. 
Structure and situation: These enzymes are either exposed at the surface (in the outer membrane) of the bacterium where they are able to come into contact with host cells and tissues or within the periplasmic space capable of being transported to the cell surface, and in outer membrane vesicles.
P. gingivalis is the only member of periodontopathic microbiota that exhibits strong dipeptidyl arylaminopeptidase activity.  Abiko et al., purified dipeptidylaminopeptidase from the spent growth supernatant of P. gingivalis and exposed it to type 1 collagen, cleaving a glycylpropyl dipeptide from the collagen protein.  Grenier and McBride were successful in localizing their aminopeptidase activity to the surface of P. gingivalis. Immunoelectron microscopy localized the enzyme in the periplasmic space. ,
Vaccine against P. gingivalis
Vaccination is a process that induces specific immune resistance to a bacterial or viral infection. A common finding in patients with periodontitis is the presence of P. gingivalis-specific antibodies in serum and gingival crevicular fluid. Immunization with several P. gingivalis-specific antigens has been shown to enhance the immune response against P. gingivalis, as demonstrated by the induction of specific antibodies and reduction of P. gingivalis-induced alveolar bone loss in animal models. The production of antibodies generally indicates the activation of our major host defense mechanism; these antibodies are insufficient to clear P. gingivalis infection. Although complete protection through immunization has not yet been achieved, new knowledge about specific P. gingivalis antigens holds promising possibilities for the future [Table 1].
|Table 1: Studies on immunization with Porphyromonas gingivalis-specific antigens|
Click here to view
| Conclusion|| |
In general, the major antigens of P. gingivalis induce an overall inflammatory immune response, as demonstrated in vitro for a wide variety of cell types and also in vivo; in experimental animal models. These data correlate with findings from studies with periodontitis patients. New research has highlighted earlier apparent contradictions in the literature demonstrating cytokine stimulation and degradation as well as cellular activation and apoptosis. These apparent contradictions can be explained by P. gingivalis antigen concentration effects, and when this is taken into account, the localized dysregulation of the immune response, that is, commonly reported can also be explained. Finally, despite the strong and active inflammatory immune response generated by P. gingivalis antigens, more research is needed to study the use of these same antigens as vaccine candidates, which, if used appropriately, may have utility as an adjunctive therapy in ameliorating chronic periodontitis.
| References|| |
Socransky SS, Haffajee AD. Dental biofilms: Difficult therapeutic targets. Periodontol 2000 2002;28:12-55.
Griffen AL, Becker MR, Lyons SR, Moeschberger ML, Leys EL. Prevalence of porphyromonas gingivalis and periodontal health status. J Clin Microbiol 1998;36:3239-42.
Kimura S, Nagai A, Onitsuka T, Koga T, Fujiwara T, Kaya H, et al
. Induction of experimental periodontitis in mice with Porphyromonas gingivalis-
J Periodontol 2000;71:1167-73.
Poulin R, Combes C. The concept of virulence: Interpretations and implications. Parasitol Today 1999;15:474-5.
Holt SC, Ebersole JL. Porphyromonas gingivalis, treponema denticola and tannerella forsythia: The "red complex", a prototype polybacterial pathogenic consortium in periodontitis. Periodontol 2000 2005;38:72-122.
Okuda K, Slots J, Genco RJ. Bacteroides gingivalis, Bacteroides asaccharolyticus, and Bacteroides melanogenicus sub-species: Cell surface morphology and adherence to erythrocytes and human buccal epithelialcells. Curr Microbiol 1981; 6:7-12.
Yoshimura F, Murakami Y, Nishikawa K, Hasegawa Y, Kawaminami S. Surface components of Porphyromonas gingivalis. J Periodontal Res 2009;44:1-12.
Evans RT, Klausen B, Sojar HT, Bedi GS, Sfintescu C, Ramamurthy NS, et al
. Immunization with Porphyromonas (Bacteroides) gingivalis fimbriae protects against periodontal destruction. Infect Immun 1992;60:2926-35.
Ogawa T, Ogo H, Kinoshita A. Antagonistic effect of synthetic peptides corresponding to the binding regions within fimbrial subunit protein for Porphyromonas gingivalis to human gingival fibroblasts. Vaccine 1997;15:230-6.
Holt SC, Kesavalu L, Walker S, Genco CA. Virulence factors of Porphyromonas gingivalis. Periodontol 2000 1999;28:168-238.
Shi Y, Ratnayake DB, Okamoto K, Abe N, Yamamoto K, Nakayama K. Genetic analyses of proteolysis, hemoglobin binding, and hemagglutination of Porphyromonas gingivalis. Construction of mutants with a combination of rgpA, rgpB, kgp, and hagA. J Biol Chem 1999;274:17955-60.
Lepine G, Progulske-Fox A. Molecular biology. In: Shah HN, Mayrand D, Genco RJ editor. Biology of the species Porphyromonas gingivalis.
Boca Raton: FL CRC Press; 1993. p. 293-319.
Duncan MJ, Emory SA, Almira EC. Porphyromonas gingivalis genes isolated by screening for epithelial cell attachment. Infect Immun 1996;64:3624-31.
Yun PL, DeCarlo AA, Collyer C, Hunter N. Modulation of an interleukin-12 and gamma interferon synergistic feedback regulatory cycle of T-cell and monocyte by cocultures by Porphyromonas gingivalis lipopolysaccharide in the absence or presence of cysteine proteinases. Infect Immun 2002;70:5695-705.
Woo DD, Holt SC, Leadbetter ER. Ultrastructure of bacteroides species: Bacteroides asaccharolyticus, Bacteroides fragilis, Bacteroides melaninogenicus subspecies melaninogenicus, and B. melaninogenicus subspecies intermedius. J Infect Dis 1979; 139:534-46.
Mansheim BJ, Kasper DL. Purification and immunochemical characterization of the outer membrane complex of Bacteroides melaninogenicus subspecies asaccharolyticus. J Infect Dis 1977;135:787-99.
Okuda K, Fukumoto Y, Takazoe I, Slots J, Genco RJ. Capsular structures of black-pigmented Bacteroides isolated from human. Bull Tokyo Dent Coll 1987;28:1-11.
Laine ML, Appelmelk BJ, van Winkelhoff AJ. Prevalence and distribution of six capsular serotypes of porphyromonas gingivalis in periodontitis patients. J Dent Res 1997;76:1840-4.
Reynolds HS, van Winkelhoff AJ, Schifferle RE, Chen PB, Zambon JJ. Relationship of encapsulation of Bacteroides gingivalis to invasiveness. J Dent Res 1989;68:328.
Sundqvist, G, Figdor D, Hanstrom L, Sorlin S, Sandstrom G. Phagocytosis and virulence of different strains of Porphyromonas gingivalis.
Scand J Dent Res 1991;99:117-29.
Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 2003;67:593-656.
Lu Q, Darveau RP, Samaranayake LP, Wang C, Jin L. Differential modulation of human(beta) defensins expression in human gingival epithelia by Porphyromonas gingivalis lipopolysaccharide with tetra- and penta-acylated lipid A structures. Innate Immun 2009;15:325-35.
Curtis MA, Kuramitsu HK, Lantz M, Macrina FL, Nakayama K, Potempa J, et al
. Molecular genetics and nomenclature of proteases of Porphyromonas gingivalis. J Periodontal Res 1999;34:464-72.
Pathirana RD, O'Brien-Simpson NM, Veith PD, Riley PF, Reynolds EC. Characterization of proteinase-adhesin complexes of Porphyromonas gingivalis. Microbiology 2006;152:2381-94.
Smalley JW, Birss AJ, Szmigielski B, Potempa J. Sequential action of R- and K-specific gingipains of Porphyromonas gingivalis in the generation of the haem-containing pigment from oxyhaemoglobin. Arch Biochem Biophys 2007;465:44-9.
Guo Y, Nguyen KA, Potempa J. Dichotomy of gingipains action as virulence factors: From cleaving substrates with the precision of a surgeon's knife to a meat chopper-like brutal degradation of proteins. Periodontol 2000 2010;54:15-44.
Potempa M, Potempa J, Kantyka T, Nguyen KA, Wawrzonek K, Manandhar SP, et al.
Interpain A, a cysteine proteinase from Prevotella intermedia, inhibits complement by degrading complement factor C3. PLOS Pathog 2009;5:e1000316.
Potempa M, Potempa J, Okroj M, Popadiak K, Eick S, Nguyen KA, et al
. Binding of complement inhibitor C4b-binding protein contributes to serum resistance of Porphyromonas gingivalis. J Immunol 2008;181:5537-44.
Matsushita K, Imamura T, Tomikawa M, Tancharoen S, Tatsuyama S, Maruyama I. DX-9065a inhibits proinflammatory events induced by gingipains and factor Xa. J Periodontal Res 2006;41:148-56.
Bedi GS, Williams T. Purification and characterization of a collagen-degrading protease from Porphyromonas gingivalis. J Biol Chem 1994;269:599-606.
Mayrand D, Grenier D. Detection of collagenase activity in oral bacteria. Can J Microbiol 1985;31:134-8.
Hoover CI, Felton JR. Nitrosoguanidine mutagenesis of B. gingivalis and isolation of protease-deficient mutants. J Dent Res 1989;67:368.
Li J, Ellen RP, Hoover CI, Felton JR. Association of proteases of Porphyromonas (Bacteroides) gingivalis with its adhesion to Actinomyces viscosus. J Dent Res 1991;70:82-6.
Takahashi N, Kato T, Kuramitsu HK. Isolation and preliminary characterization of the Porphyromonas gingivalis prtC gene expressing collagenase activity. FEMS Microbiol Lett 1991; 68:135-8.
Suido H, Nakamura M, Mashimo PA, Zambon JJ, Genco RJ. Arylaminopeptidase activities of oral bacteria. J Dent Res 1986;65:1335-40.
Abiko Y, Hayakawa M, Murai S, Takiguchi H. Glycylprolyl dipeptidylaminopeptidase from Bacteroides gingivalis.
J Dent Res 1985;64:106-11.
Grenier D, McBride BC. Isolation of a membrane-associated Bacteroides gingivalis glycylprolyl protease. Infect Immun 1987; 55:3131-6.
Choi JI, Schifferle RE, Yoshimura F, Kim BW. Capsular polysaccharide-fimbrial protein conjugate vaccine protects against Porphyromonas gingivalis infection in SCID mice reconstituted with human peripheral blood lymphocytes. Infect Immun 1998;66:391-3.
Gonzalez D, Tzianabos AO, Genco CA, Gibson FC 3rd. Immunization with Porphyromonas gingivalis capsular polysaccharide prevents P. gingivalis-elicited oral bone loss in a murine model. Infect Immun 2003;71:2283-7.
Elkins KL, Stashak PW, Baker PJ. Prior exposure to subimmunogenic amounts of some bacterial lipopolysaccharides induces specific immunological unresponsiveness. Infect Immun 1987;55:3085-92.
Chen PB, Davern LB, Schifferle R, Zambon JJ. Protective immunization against experimental Bacteroides (Porphyromonas) gingivalis infection. Infect Immun 1990;58:3394-400.
Kawabata S, Terao Y, Fujiwara T, Nakagawa I, Hamada S. Targeted salivary gland immunization with plasmid DNA elicits specific salivary immunoglobulin A and G antibodies and serum immunoglobulin G antibodies in mice. Infect Immun 1999;67:5863-8.
Nagasawa T, Aramaki M, Takamatsu N, Koseki T, Kobayashi H, Ishikawa I. Oral administration of Porphyromonas gingivalis fimbriae with cholera toxin induces anti-fimbriae serum IgG, IgM, IgA and salivary IgA antibodies. J Periodontal Res 1999;34:169-74.
Fan Q, Sims T, Sojar H, Genco R, Page RC. Fimbriae of Porphyromonas gingivalis induce opsonic antibodies that significantly enhance phagocytosis and killing by human polymorphonuclear leukocytes. Oral Microbiol Immunol 2001;16:144-52.
Sharma A, Honma K, Evans RT, Hruby DE, Genco RJ. Oral immunization with recombinant Streptococcus gordonii expressing Porphyromonas gingivalis FimA domains. Infect Immun 2001;69:2928-34.
Guo H, Wang X, Jiang G, Yang P. Construction of a sIgA-enhancing anti-Porphyromonas gingivalis FimA vaccine and nasal immunization in mice. Immunol Lett 2006;107:71-5.
Takahashi Y, Kumada H, Hamada N, Haishima Y, Ozono S, Isaka M, et al.
Induction of immune responses and prevention of alveolar bone loss by intranasal administration of mice with Porphyromonas gingivalis fimbriae and recombinant cholera toxin B subunit. Oral Microbiol Immunol 2007;22:374-80.
Ross BC, Czajkowski L, Vandenberg KL, Camuglia S, Woods J, Agius C, et al.
Characterization of two outer membrane protein antigens of Porphyromonas gingivalis that are protective in a murine lesion model. Oral Microbiol Immunol 2004;19:6-15.
Namikoshi J, Otake S, Maeba S, Hayakawa M, Abiko Y, Yamamoto M. Specific antibodies induced by nasally administered 40-kDa outer membrane protein of Porphyromonas gingivalis inhibits coaggregation activity of P. gingivalis. Vaccine 2003;22:250-6.
Maeba S, Otake S, Namikoshi J, Shibata Y, Hayakawa M, Abiko Y, et al
. Transcutaneous immunization with a 40-kDa outer membrane protein of Porphyromonas gingivalis induces specific antibodies which inhibit coaggregation by P. gingivalis. Vaccine 2005;23:2513-21.
Hamada N, Watanabe K, Tahara T, Nakazawa K, Ishida I, Shibata Y, et al.
The r40-kDa outer membrane protein human monoclonal antibody protects against Porphyromonas gingivalis-induced bone loss in rats. J Periodontol 2007;78:933-9.
Koizumi Y, Kurita-Ochiai T, Yamamoto M. Transcutaneous immunization with an outer membrane protein of Porphyromonas gingivalis without adjuvant elicits marked antibody responses. Oral Microbiol Immunol 2008;23:131-8.
Momoi F, Hashizume T, Kurita-Ochiai T, Yuki Y, Kiyono H, Yamamoto M. Nasal vaccination with the 40-kilodalton outer membrane protein of Porphyromonas gingivalis and a nontoxic chimeric enterotoxin adjuvant induces long-term protective immunity with reduced levels of immunoglobulin E antibodies. Infect Immun 2008;76:2777-84.
Zhang T, Hashizume T, Kurita-Ochiai T, Yamamoto M. Sublingual vaccination with outer membrane protein of Porphyromonas gingivalis and Flt3 ligand elicits protective immunity in the oral cavity. Biochem Biophys Res Commun 2009;390:937-41.
Genco CA, Odusanya BM, Potempa J, Mikolajczyk-Pawlinska J, Travis J. A peptide domain on gingipain R which confers immunity against Porphyromonas gingivalis infection in mice. Infect Immun 1998;66:4108-14.
O'Brien-Simpson NM, Paolini RA, Reynolds EC. RgpA-Kgp peptide-based immunogens provide protection against Porphyromonas gingivalis challenge in a murine lesion model. Infect Immun 2000;68:4055-63.
Gibson FC, Genco CA. Prevention of Porphyromonas gingivalis-induced oral bone loss following immunization with gingipain R1. Infect Immun 2001;69:7959-63.
Kuboniwa M, Amano A, Shizukuishi S, Nakagawa I, Hamada S. Specific antibodies to Porphyromonas gingivalis Lys-gingipain by DNA vaccination inhibit bacterial binding to hemoglobin and protect mice from infection. Infect Immun 2001;69:2972-9.
Yonezawa H, Ishihara K, Okuda K. Arg-gingipain a DNA vaccine induces protective immunity against infection by Porphyromonas gingivalis in a murine model. Infect Immun 2001;69:2858-64.
O'Brien-Simpson NM, Pathirana RD, Paolini RA, Chen YY, Veith PD, Tam V, et al
. An immune response directed to proteinase and adhesin functional epitopes protects against Porphyromonas gingivalis-induced periodontal bone loss. J Immunol 2005;175:3980-9.
Frazer LT, O'Brien-Simpson NM, Slakeski N, Walsh KA, Veith PD, Chen CG, et al.
Vaccination with recombinant adhesins from the RgpA- Kgp proteinase-adhesin complex protects against Porphyromonas gingivalis infection. Vaccine 2006;24:6542-54.
Miyachi K, Ishihara K, Kimizuka R, Okuda K. Arg-gingipain A DNA vaccine prevents alveolar bone loss in mice. J Dent Res 2007;86:446-50.
Page RC, Lantz MS, Darveau R, Jeffcoat M, Mancl L, Houston L, et al
. Immunization of Macaca fascicularis against experimental periodontitis using a vaccine containing cysteine proteases purified from Porphyromonas gingivalis. Oral Microbiol Immunol 2007;22:162-8.
Katz J, Black KP, Michalek SM. Host responses to recombinant hemagglutinin B of Porphyromonas gingivalis in an experimental rat model. Infect Immun 1999;67:4352-9.
Yang QB, Martin M, Michalek SM, Katz J. Mechanisms of monophosphoryl lipid A augmentation of host responses to recombinant HagB from Porphyromonas gingivalis. Infect Immun 2002;70:3557-65.
Shibata Y, Hosogi Y, Hayakawa M, Hori N, Kamada M, Abiko Y. Construction of novel human monoclonal antibodies neutralizing Porphyromonas gingivalis hemagglutination activity using transgenic mice expressing human Ig loci. Vaccine 2005;23:3850-6.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
|This article has been cited by|
||Exacerbation of AMD Phenotype in Lasered CNV Murine Model by Dysbiotic Oral Pathogens
| ||Pachiappan Arjunan,Radhika Swaminathan,Jessie Yuan,Mohamed Elashiry,Amany Tawfik,Mohamed Al-Shabrawey,Pamela M. Martin,Thangaraju Muthusamy,Christopher W. Cutler |
| ||Antioxidants. 2021; 10(2): 309 |
|[Pubmed] | [DOI]|
||Eye on the Enigmatic Link: Dysbiotic Oral Pathogens in Ocular Diseases; The Flip Side
| ||Pachiappan Arjunan |
| ||International Reviews of Immunology. 2020; : 1 |
|[Pubmed] | [DOI]|
||Effect of curcumin on growth, biofilm formation and virulence factor gene expression of Porphyromonas gingivalis
| ||Vijay M. Kumbar,Malleswara Rao Peram,Manohar S. Kugaji,Tejas Shah,Sanjivani P. Patil,Uday M. Muddapur,Kishore G. Bhat |
| ||Odontology. 2020; |
|[Pubmed] | [DOI]|
||Marine bromophenols as an effective inhibitor of virulent proteins (peptidyl arginine deiminase, gingipain R and hemagglutinin A) in Porphyromas gingivalis
| ||Chikoo Cherian,J. Jannet Vennila,Leena Sharan |
| ||Archives of Oral Biology. 2019; 100: 119 |
|[Pubmed] | [DOI]|
||Presence of Porphyromonas and Prevotella species in the oral microflora of cattle with periodontitis
| ||Ana Carolina Borsanelli,Elerson Gaetti-Jardim Júnior,Christiane Marie Schweitzer,Jürgen Döbereiner,Iveraldo S. Dutra |
| ||Pesquisa Veterinária Brasileira. 2015; 35(10): 829 |
|[Pubmed] | [DOI]|