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Biomedical subjects

C A Genco

Publications and source records attributed to C A Genco.

At least 19 recordsLinked to original sources
PubMed2006

Innate immune signaling and Porphyromonas gingivalis-accelerated atherosclerosis.

Periodontal diseases are a group of diseases that lead to erosion of the hard and soft tissues of the periodontium, which, in severe cases, can result in tooth loss. Anecdotal clinical observations have suggested that poor oral health may be associated with poor systemic health; however, only recently have appropriate epidemiological studies been initiated, with defined clinical endpoints of periodontal disease, to address the association of periodontal disease with increased risk for cardiovascular and cerebrovascular disease. Although conflicting reports exist, these epidemiological studies support this connection. Paralleling these epidemiological studies, emerging basic scientific studies also support that infection may represent a risk factor for atherosclerosis. With P. gingivalis as a model pathogen, in vitro studies support that this organism can activate host innate immune responses associated with atherosclerosis, and in vivo studies demonstrate that this organism can accelerate atheroma deposition in animal models. In this review, we focus primarily on the basic scientific studies performed to date which support that infection with bacteria, most notably P. gingivalis, accelerates atherosclerosis. Furthermore, we attempt to bring together these studies to provide an up-to-date framework of emerging theories into the mechanisms underlying periodontal disease and increased risk for atherosclerosis, as well as identify intervention strategies to reduce the incidence of periodontal disease in humans, in an attempt to decrease risk for systemic complications of periodontal disease such as atherosclerotic cardiovascular disease.

Animals↗
PubMed2005

Inducible nitric oxide synthase mediates bone development and P. gingivalis-induced alveolar bone loss.

The role of inducible nitric oxide synthase (iNOS) in bone development and bacterially induced periodontal bone loss was examined using mice with targeted mutation of the iNOS gene. Femurs of iNOS KO mice showed 30% and 9% higher bone mineral density compared to wild type (WT) at 4 and 9 weeks of age, respectively. Micro-computed tomography revealed that cortical thickness and cortical bone density is increased in the absence of iNOS, while trabecular bone thickness and bone density remains unchanged. Histochemical analysis using TRAP staining showed that osteoclast numbers are lower by 25% in iNOS KO femurs compared to WT femurs. When bone marrow cells were stimulated with M-CSF and RANKL in vitro, iNOS KO cultures developed 51% fewer TRAP-positive multinuclear cells compared to WT cultures. When similar cultures were grown on dentine discs, resorption pit area was decreased by 54% in iNOS KO cultures. Gene expression studies showed that iNOS expression is induced by M-CSF and RANKL in WT bone marrow cultures, while no iNOS transcript was detected in iNOS KO. No compensatory change was detected in the expression of neuronal or endothelial NOS isoforms. There was no difference in RANK and osteoprotegerin expression between iNOS KO and WT bone marrow cultures after M-CSF and RANKL-treatment, while Traf6 expression was significantly lower in the absence of iNOS. In the alveolar bone of the maxilla, the distance between the cementoenamel junction and the alveolar bone crest was larger in iNOS KO compared to WT mice from 6 to 14 weeks of age, indicating a developmental effect of iNOS in oral tissues. Oral administration of the periodontal pathogen Porphyromonas gingivalis caused alveolar bone loss in the maxilla of WT mice, but failed to do so in iNOS KO mice. Expression of the osteoclast marker cathepsin K was 25% lower in iNOS KO alveolar bone. These data indicate that iNOS promotes bone resorption during bone development as well as after bacterial infection, and that iNOS is an important signal for normal osteoclast differentiation.

Alveolar Bone Loss↗
PubMed2001

Emerging strategies in microbial haem capture.

Gram-negative pathogenic bacteria have evolved novel strategies to obtain iron from host haem-sequestering proteins. These include the production of specific outer membrane receptors that bind directly to host haem-sequestering proteins, secreted haem-binding proteins (haemophores) that bind haem/haemoglobin/haemopexin and deliver the complex to a bacterial cell surface receptor and bacterial proteases that degrade haem-sequestering proteins. Once removed from haem-sequestering proteins, haem may be transported via the bacterial outer membrane receptor into the cell. Recent studies have begun to define the steps by which haem is removed from bacterial haem proteins and transported into the cell. This review describes recent work on the discovery and characterization of these systems. Reference is also made to the transport of haem in serum (via haemoglobin, haemoglobin/haptoglobin, haemopexin, albumin and lipoproteins) and to mechanisms of iron removal from the haem itself (probably via a haem oxygenase pathway in which the protoporphyrin ring is degraded). Haem protein-receptor interactions are discussed in terms of the criteria that govern protein-protein interactions in general, and connections between haem transport and the emerging field of metal transport via metallochaperones are outlined.

Bacterial Proteins↗
PubMed2001

Prevention of Porphyromonas gingivalis-induced oral bone loss following immunization with gingipain R1.

The arginine gingipains RgpA and RgpB of Porphyromonas gingivalis are well-documented virulence factors of this organism. Structurally, RgpA and RgpB have nearly identical catalytic domains, while RgpA possesses an additional hemagglutinin domain. In this study, we examined the abilities of these proteins to elicit protection against P. gingivalis-mediated oral bone loss in a murine oral challenge model. Mice immunized subcutaneously with heat-killed P. gingivalis or purified RgpA or RgpB possessed elevated levels of P. gingivalis-specific immunoglobulin G; however, only the animals immunized with P. gingivalis whole cells or RgpA were protected from maxillary bone loss. These data suggest that immunization with RgpA stimulates the production of hemagglutinin domain-specific antibodies, which contribute to the prevention of P. gingivalis-mediated periodontal disease.

Adhesins, Bacterial↗
PubMed2001

Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells.

In this study we utilized immortalized morphologically and functionally distinct epithelial cell lines from normal human endocervix, ectocervix, and vagina to characterize gonococcal epithelial interactions pertinent to the lower female genital tract. Piliated, but not nonpiliated, N. gonorrhoeae strain F62 variants actively invaded these epithelial cell lines, as demonstrated by an antibiotic protection assay and confocal microscopy. Invasion of these cells by green fluorescent protein-expressing gonococci was characterized by colocalization of gonococci with F actin, which were initially detected 30 min postinfection. In all three cell lines, upregulation of interleukin 8 (IL-8) and IL-6, intercellular adhesion molecule 1 (CD54), and the nonspecific cross-reacting antigen (CD66c) were detected 4 h after infection with piliated and nonpiliated gonococci. Furthermore, stimulation of all three cell lines with gonococcal whole-cell lysates resulted in a similar upregulation of IL-6 and IL-8, confirming that bacterial uptake is not essential for this response. Increased levels of IL-1 were first detected 8 h after infection with gonococci, suggesting that the earlier IL-8 and IL-6 responses were not mediated through the IL-1 signaling pathway. The IL-1 response was limited to cultures infected with piliated gonococci and was more vigorous in the endocervical epithelial cells. The ability of gonococci to stimulate distinct proinflammatory host responses in these morphologically and functionally different compartments of the lower female genital tract may contribute directly to the inflammatory signs and symptoms characteristic of disease caused by N. gonorrhoeae.

Cell Line, Transformed↗
PubMed2001

Binding specificity of the Porphyromonas gingivalis heme and hemoglobin receptor HmuR, gingipain K, and gingipain R1 for heme, porphyrins, and metalloporphyrins.

Previous genetic and biochemical studies have confirmed that hemoglobin and hemin utilization in Porphyromonas gingivalis is mediated by the outer membrane hemoglobin and heme receptor HmuR, as well as gingipain K (Kgp), a lysine-specific cysteine protease, and gingipain R1 (HRgpA), one of two arginine-specific cysteine proteases. In this study we report on the binding specificity of the recombinant P. gingivalis HmuR protein and native gingipains for hemoglobin, hemin, various porphyrins, and metalloporphyrins as assessed by spectrophotometric assays, by affinity chromatography, and by enzyme-linked immunosorbent assay. Protoporphyrin, mesoporphyrin, deuteroporphyrin, hematoporphyrin, and some of their iron, copper, and zinc derivatives were examined to evaluate the role of both the central metal ion and the peripheral substituents on binding to recombinant HmuR and soluble gingipains. Scatchard analysis of hemin binding to Escherichia coli cells expressing recombinant membrane-associated six-His-tagged HmuR yielded a linear plot with a binding affinity of 2.4 x 10(-5) M. Recombinant E. coli cells bound the iron, copper, and zinc derivatives of protoporphyrin IX (PPIX) with similar affinities, and approximately four times more tightly than PPIX itself, which suggests that the active site of HmuR contains a histidine that binds the metal ion in the porphyrin ring. Furthermore, we found that recombinant HmuR prefers the ethyl and vinyl side chains of the PPIX molecule to either the larger hydroxyethyl or smaller hydrogen side chains. Kgp and HRgpA were demonstrated to bind various porphyrins and metalloporphyrins with affinities similar to those for hemin, indicating that the binding of Kgp and HRgpA to these porphyrins does not require a metal within the porphyrin ring. We did not detect the binding of RgpB, the arginine-specific cysteine protease that lacks a C-terminal hemagglutinin domain, to hemoglobin, porphyrins, or metalloporphyrins. Kgp and HRgpA, but not RgpB, were demonstrated to bind directly to soluble recombinant six-His-tagged HmuR. Several possible mechanisms for the cooperation between outer membrane receptor HmuR and proteases Kgp and HRgpA in hemin and hemoglobin binding and utilization are discussed.

Adhesins, Bacterial↗
PubMed2001

Degradation of host heme proteins by lysine- and arginine-specific cysteine proteinases (gingipains) of Porphyromonas gingivalis.

Porphyromonas gingivalis can use hemoglobin bound to haptoglobin and heme complexed to hemopexin as heme sources; however, the mechanism by which hemin is released from these proteins has not been defined. In the present study, using a variety of analytical methods, we demonstrate that lysine-specific cysteine proteinase of P. gingivalis (gingipain K, Kgp) can efficiently cleave hemoglobin, hemopexin, haptoglobin, and transferrin. Degradation of hemopexin and transferrin in human serum by Kgp was also detected; however, we did not observe extensive degradation of hemoglobin in serum by Kgp. Likewise the beta-chain of haptoglobin was partially protected from degradation by Kgp in a haptoglobin-hemoglobin complex. Arginine-specific gingipains (gingipains R) were also found to degrade hemopexin and transferrin in serum; however, this was observed only at relatively high concentrations of these enzymes. Growth of P. gingivalis strain A7436 in a minimal media with normal human serum as a source of heme correlated not only with the ability of the organism to degrade hemoglobin, haptoglobin, hemopexin, and transferrin but also with an increase in gingipain K and gingipain R activity. The ability of gingipain K to cleave hemoglobin, haptoglobin, and hemopexin may provide P. gingivalis with a usable source of heme for growth and may contribute to the proliferation of P. gingivalis within periodontal pockets in which erythrocytes are abundant.

Adhesins, Bacterial↗
PubMed2000

Environmental cues and gene expression in Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.

Microorganisms typically adapt to environmental cues by turning on and off the expression of virulence genes which, in turn, allows for optimal growth and survival within different environmental niches. This adaptation strategy includes sensing and responding to changes in nutrients, pH, temperature, oxygen tension, redox potential, microbial flora, and osmolarity. For a bacterium to adhere to, penetrate, replicate in, and colonize host cells, it is critical that virulence genes are expressed during certain periods of the infection process. Thus, throughout the different stages of an infection, different sets of virulence factors are turned on and off in response to different environmental signals, allowing the bacterium to effectively adapt to its varying niche. In this review, we focus on the regulation of virulence gene expression in two pathogens which have been implicated as major etiological agents in adult and juvenile periodontal diseases: Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans. Understanding the mechanisms of virulence gene expression in response to the local environment of the host will provide crucial information in the development of effective treatments targeted at eradication of these periodontal disease pathogens.

Adaptation, Physiological↗
PubMed2000

Pathogenic neisseriae can use hemoglobin, transferrin, and lactoferrin independently of the tonB locus.

Redundant TonB systems which function in iron transport from TonB-dependent ligands have recently been identified in several gram-negative bacteria. We demonstrate here that in addition to the previously described tonB locus, an alternative system exists for the utilization of iron from hemoglobin, transferrin, or lactoferrin in Neisseria meningitidis and Neisseria gonorrhoeae. Following incubation on media containing hemoglobin, N. meningitidis IR3436 (tonB exbB exbD deletion mutant) and N. gonorrhoeae PD3401 (tonB insertional mutant) give rise to colonies which can grow with hemoglobin. Transfer of Hb(+) variants (PD3437 or PD3402) to media containing hemoglobin, transferrin, and/or lactoferrin as sole iron sources resulted in growth comparable to that observed for the wild-type strains. Transformation of N. meningitidis IR3436 or N. gonorrhoeae PD3401 with chromosomal DNA from the Hb(+) variants yielded transformants capable of growth with hemoglobin. When we inactivated the TonB-dependent outer membrane hemoglobin receptors (HmbR or HpuB) in the Neisseria Hb(+) variants, these strains could not grow with hemoglobin; however, growth was observed with transferrin and/or lactoferrin. These results demonstrate that accumulation of iron from hemoglobin, transferrin, and lactoferrin in the pathogenic neisseriae can occur via a system that is independent of the previously described tonB locus.

Bacterial Outer Membrane Proteins↗
PubMed2000

Characterization and expression of HmuR, a TonB-dependent hemoglobin receptor of Porphyromonas gingivalis.

The gram-negative pathogen Porphyromonas gingivalis requires hemin for growth. Hemoglobin bound to haptoglobin and hemin complexed to hemopexin can be used as heme sources, indicating that P. gingivalis must have a means to remove the hemin from these host iron-binding proteins. However, the specific mechanisms utilized by P. gingivalis for the extraction of heme from heme-binding proteins and for iron transport are poorly understood. In this study we have determined that a newly identified TonB-dependent hemoglobin-hemin receptor (HmuR) is involved in hemoglobin binding and utilization in P. gingivalis A7436. HmuR shares amino acid homology with TonB-dependent outer membrane receptors of gram-negative bacteria involved in the acquisition of iron from hemin and hemoglobin, including HemR of Yersinia enterocolitica, ShuA of Shigella dysenteriae, HpuB of Neisseria gonorrhoeae and N. meningitidis, HmbR of N. meningitidis, HgbA of Haemophilus ducreyi, and HgpB of H. influenzae. Southern blot analysis confirmed the presence of the hmuR gene and revealed genetic variability in the carboxy terminus of hmuR in P. gingivalis strains 33277, 381, W50, and 53977. We also identified directly upstream of the hmuR gene a gene which we designated hmuY. Upstream of the hmuY start codon, a region with homology to the Fur binding consensus sequence was identified. Reverse transcription-PCR analysis revealed that hmuR and hmuY were cotranscribed and that transcription was negatively regulated by iron. Inactivation of hmuR resulted in a decreased ability of P. gingivalis to bind hemoglobin and to grow with hemoglobin or hemin as sole iron sources. Escherichia coli cells expressing recombinant HmuR were shown to bind hemoglobin and hemin. Furthermore, purified recombinant HmuR was demonstrated to bind hemoglobin. Taken together, these results indicate that HmuR serves as the major TonB-dependent outer membrane receptor involved in the utilization of both hemin and hemoglobin in P. gingivalis.

Amino Acid Sequence↗
PubMed1999

Antiviral effects of synthetic membrane-active peptides on herpes simplex virus, type 1.

Magainins are cationic peptides with antimicrobial activity which were originally isolated from the skin of the African clawed frog (Xenopus laevis). Several synthetic derivatives of this class of peptides were evaluated for antiviral activity against herpes simplex virus, type 1 (HSV). Some of the peptides (MSI-102, -248, -420, -499/500 combination, -591, -594, and -1251) showed significant reduction of HSV plaque-forming units. The antiviral effect was enhanced when HSV was pretreated with the peptides prior to inoculation onto Vero monolayers, suggesting a direct effect on the virion. Most of the peptides with anti-HSV activity were lysine-rich, and the addition of octanoyl groups to the peptides appeared to enhance the antiviral effect.

Amino Acid Sequence↗
PubMed1999

Role of gingipains R in the pathogenesis of Porphyromonas gingivalis-mediated periodontal disease.

It has been demonstrated that the Porphyromonas gingivalis cysteine proteinases (gingipains) activate and/or degrade a broad range of host proteins. Inactivation of gingipains R prior to infection of mice results in a decrease in the virulence of P. gingivalis. Analysis of mouse, rabbit, and chicken antisera raised to gingipain R1 demonstrated that the hemagglutinin domains of gingipains are very immunogenic; however, immunization of mice with a peptide derived from the hemagglutinin domain did not protect mice from P. gingivalis infection. Our recent studies indicate that immunization of mice with a peptide corresponding to the N-terminus of the catalytic domain of gingipains R results in the generation of an immune response that affords protection of mice from P. gingivalis infection. It is postulated that the protection observed results from the inactivation of the enzymatic activity of gingipains R as a result of antibody recognition of a processing site on the gingipain R precursor.

Adhesins, Bacterial↗
PubMed1999

Transposition of the endogenous insertion sequence element IS1126 modulates gingipain expression in Porphyromonas gingivalis.

We have previously reported on a Tn4351-generated mutant of Porphyromonas gingivalis (MSM-3) which expresses enhanced arginine-specific proteinase activity and does not utilize hemin or hemoglobin for growth (C. A. Genco et al., Infect. Immun. 63:2459-2466, 1995). In the process of characterizing the genetic lesion in P. gingivalis MSM-3, we have determined that the endogenous P. gingivalis insertion sequence element IS1126 is capable of transposition within P. gingivalis. We have also determined that IS1126 transposition modulates the transcription of the genes encoding the lysine-specific proteinase, gingipain K (kgp) and the arginine-specific proteinase, gingipain R2 (rgpB). Sequence analysis of P. gingivalis MSM-3 revealed that Tn4351 had inserted 60 bp upstream of the P. gingivalis endogenous IS element IS1126. Furthermore, P. gingivalis MSM-3 exhibited two additional copies of IS1126 compared to the parental strain A7436. Examination of the first additional IS1126 element, IS1126(1), indicated that it has inserted into the putative promoter region of the P. gingivalis kgp gene. Analysis of total RNA extracted from P. gingivalis MSM-3 demonstrated no detectable kgp transcript; likewise, P. gingivalis MSM-3 was devoid of lysine-specific proteinase activity. The increased arginine-specific proteinase activity exhibited by P. gingivalis MSM-3 was demonstrated to correlate with an increase in the rgpA and rgpB transcripts. The second additional IS1126 element, IS1126(2), was found to have inserted upstream of a newly identified gene, hmuR, which exhibits homology to a number of TonB-dependent genes involved in hemin and iron acquisition. Analysis of total RNA from P. gingivalis MSM-3 demonstrated that hmuR is transcribed, indicating that the insertion of IS1126 had not produced a polar effect on hmuR transcription. The hemin-hemoglobin defect in P. gingivalis MSM-3 is proposed to result from the inactivation of Kgp, which has recently been demonstrated to function in hemoglobin binding. Taken together, the results presented here demonstrate that the introduction of Tn4351 into the P. gingivalis chromosome has resulted in two previously undocumented phenomena in P. gingivalis: (i) the transposition of the endogenous insertion sequence element IS1126 and (ii) the modulation of gingipain transcription and translation as a result of IS1126 transposition.

Adhesins, Bacterial↗
PubMed1999

FbpC is not essential for iron acquisition in Neisseria gonorrhoeae.

The fbpABC locus of Neisseria gonorrhoeae has been proposed to encode a periplasmic protein-dependent iron transport system. Although the function of the gonococcal FbpA protein has been well characterized and its role as a periplasmic binding protein is well defined, little is known about the function of the FbpB and FbpC proteins. To define the function of the gonococcal FbpC protein, an N. gonorrhoeae F62 fbpC mutant was constructed by insertional inactivation with the kanamycin gene. The N. gonorrhoeae F62 fbpC mutant was observed to grow with heme, transferrin, or ferric nitrate as the sole exogenous iron source, indicating that the gonococcal FbpC protein is not absolutely required for growth with these iron sources. In previous studies we were unable to detect fbpB- or fbpC-specific transcripts by Northern analysis. Reverse transcription-PCR analysis with RNA obtained from N. gonorrhoeae F62 grown under iron-replete and -depleted conditions detected fbpA and fbpAB transcripts but failed to detect fbpC or fbpBC transcripts. These results indicate that FbpC does not play a pivotal role in iron transport in N. gonorrhoeae and suggest that additional ABC transport systems are functional in the gonococcus for the acquisition of iron.

Bacterial Proteins↗
PubMed1998

Animal models for Porphyromonas gingivalis-mediated periodontal disease.

Porphyromonas gingivalis is one of the principal pathogens in the development of adult periodontitis. Several different animal models have been used to evaluate the complex interactions between P. gingivalis and the host and these have been an important research tool for studying the pathogenesis of P. gingivalis-mediated periodontal diseases.

Adult↗
PubMed1998

Invasion of aortic and heart endothelial cells by Porphyromonas gingivalis.

Invasion of host cells is believed to be an important strategy utilized by a number of pathogens, which affords them protection from the host immune system. The connective tissues of the periodontium are extremely well vascularized, which allows invading microorganisms, such as the periodontal pathogen Porphyromonas gingivalis, to readily enter the bloodstream. However, the ability of P. gingivalis to actively invade endothelial cells has not been previously examined. In this study, we demonstrate that P. gingivalis can invade bovine and human endothelial cells as assessed by an antibiotic protection assay and by transmission and scanning electron microscopy. P. gingivalis A7436 was demonstrated to adhere to and to invade fetal bovine heart endothelial cells (FBHEC), bovine aortic endothelial cells (BAEC), and human umbilical vein endothelial cells (HUVEC). Invasion efficiencies of 0.1, 0.2, and 0. 3% were obtained with BAEC, HUVEC, and FBHEC, respectively. Invasion of FBHEC and BAEC by P. gingivalis A7436 assessed by electron microscopy revealed the formation of microvillus-like extensions around adherent bacteria followed by the engulfment of the pathogen within vacuoles. Invasion of BAEC by P. gingivalis A7436 was inhibited by cytochalasin D, nocodazole, staurosporine, protease inhibitors, and sodium azide, indicating that cytoskeletal rearrangements, protein phosphorylation, energy metabolism, and P. gingivalis proteases are essential for invasion. In contrast, addition of rifampin, nalidixic acid, and chloramphenicol had little effect on invasion, indicating that bacterial RNA, DNA, and de novo protein synthesis are not required for P. gingivalis invasion of endothelial cells. Likewise de novo protein synthesis by endothelial cells was not required for invasion by P. gingivalis. P. gingivalis 381 was demonstrated to adhere to and to invade BAEC (0.11 and 0.1% efficiency, respectively). However, adherence and invasion of the corresponding fimA mutant DPG3, which lacks the major fimbriae, was not detected. These results indicate that P. gingivalis can actively invade endothelial cells and that fimbriae are required for this process. P. gingivalis invasion of endothelial cells may represent another strategy utilized by this pathogen to thwart the host immune response.

Animals↗
PubMed1998

A peptide domain on gingipain R which confers immunity against Porphyromonas gingivalis infection in mice.

The cysteine proteinases referred to as gingipains R (gingipain R1 and gingipain R2) and gingipain K produced by Porphyromonas gingivalis are virulence factors of this periodontal pathogen which likely act by interrupting host defense mechanisms and by participating in the penetration and destruction of host connective tissue. To examine the effect of immunization with gingipains R on the ability of P. gingivalis to colonize and invade in the mouse chamber model, BALB/c mice were immunized intraperitoneally with the 95-kDa gingipain R1, the 50-kDa gingipain R2, or multiple antigenic peptide (MAP)-conjugated gingipain R-derived peptides and then challenged with P. gingivalis. Immunization of mice with the 95-kDa gingipain R1, the 50-kDa gingipain R2, or a peptide derived from the N-terminal sequence of the catalytic domain of gingipains R (peptide A) followed by challenge with P. gingivalis A7436 resulted in protection from P. gingivalis invasion. In contrast, immunization with peptides corresponding to either a sequence encompassing the catalytic cysteine residue of gingipains R (peptide B) or an identical sequence within the catalytic domains of gingipain R1 and gingipain K (peptide C), followed by challenge with P. gingivalis, did not protect animals, nor did immunization with a peptide corresponding to sequences within the adhesion/hemagglutinin domain of gingipain R1 (peptide D) which have been shown to be directly involved in the hemagglutinin activity of gingipain R1. However, the immunoglobulin G (IgG) titer obtained following immunization with peptide D was comparable to that obtained following immunization with the N-terminal peptide (peptide A). Competitive enzyme-linked immunosorbent assays, using either the 95-kDa gingipain R1 or gingipain K as the competing soluble antigen, indicated that 42 and 53% of the antibodies induced by immunization with heat-killed bacteria recognize gingipain R1 and gingipain K, respectively; however, even at very high concentrations, the 50-kDa gingipain R2 did not hinder IgG binding to P. gingivalis. These results indicate that antibodies directed to the amino-terminal region of the catalytic domain of gingipains R are capable of inducing a protective immune response against P. gingivalis infection in the mouse chamber model.

Adhesins, Bacterial↗