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      The lysine gingipain adhesin domains from Porphyromonas gingivalis interact with erythrocytes and albumin: Structures correlate to function

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          The crystal structure of the K1 domain, an adhesin module of the lysine gingipain (Kgp) expressed on the cell surface by the periodontopathic anaerobic bacterium, Porphyromonas gingivalis W83, is compared to the previously determined structures of homologues K2 and K3, all three being representative members of the cleaved adhesin domain family. In the structure of K1, the conformation of the most extensive surface loop is unexpectedly perturbed, perhaps by crystal packing, and is displaced from a previously reported arginine-anchored position observed in K2 and K3. This displacement allows the loop to become free to interact with other proteins; the alternate flipped-out loop conformation is a novel mechanism for interacting with target host proteins, other bacteria, or other gingipain protein domains. Further, the K1 adhesin module, like others, is found to be haemolytic in vitro, and so, functions in erythrocyte recognition thereby contributing to the haemolytic function of Kgp. K1 was also observed to selectively bind to haem-albumin with high affinity, suggesting this domain may be involved in gingipain-mediated haem acquisition from haem-albumin. Therefore, it is most likely that all cleaved adhesin domains of Kgp contribute to the pathogenicity of P. gingivalis in more complex ways than simply mediating bacterial adherence.

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          Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis.

          Porphyromonas gingivalis, a gram-negative anaerobe, is a major etiological agent in the initiation and progression of severe forms of periodontal disease. An opportunistic pathogen, P. gingivalis can also exist in commensal harmony with the host, with disease episodes ensuing from a shift in the ecological balance within the complex periodontal microenvironment. Colonization of the subgingival region is facilitated by the ability to adhere to available substrates such as adsorbed salivary molecules, matrix proteins, epithelial cells, and bacteria that are already established as a biofilm on tooth and epithelial surfaces. Binding to all of these substrates may be mediated by various regions of P. gingivalis fimbrillin, the structural subunit of the major fimbriae. P. gingivalis is an asaccharolytic organism, with a requirement for hemin (as a source of iron) and peptides for growth. At least three hemagglutinins and five proteinases are produced to satisfy these requirements. The hemagglutinin and proteinase genes contain extensive regions of highly conserved sequences, with posttranslational processing of proteinase gene products contributing to the formation of multimeric surface protein-adhesin complexes. Many of the virulence properties of P. gingivalis appear to be consequent to its adaptations to obtain hemin and peptides. Thus, hemagglutinins participate in adherence interactions with host cells, while proteinases contribute to inactivation of the effector molecules of the immune response and to tissue destruction. In addition to direct assault on the periodontal tissues, P. gingivalis can modulate eucaryotic cell signal transduction pathways, directing its uptake by gingival epithelial cells. Within this privileged site, P. gingivalis can replicate and impinge upon components of the innate host defense. Although a variety of surface molecules stimulate production of cytokines and other participants in the immune response, P. gingivalis may also undertake a stealth role whereby pivotal immune mediators are selectively inactivated. In keeping with its strict metabolic requirements, regulation of gene expression in P. gingivalis can be controlled at the transcriptional level. Finally, although periodontal disease is localized to the tissues surrounding the tooth, evidence is accumulating that infection with P. gingivalis may predispose to more serious systemic conditions such as cardiovascular disease and to delivery of preterm infants.
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            The prevalence and incidence of coronary heart disease is significantly increased in periodontitis: a meta-analysis.

            Previous studies have shown conflicting results as to whether periodontitis (PD) is associated with increased risk of coronary heart disease (CHD). The aim of the current study was to evaluate whether such an association exists. A systematic review of the literature revealed 5 prospective cohort studies (follow-up >6 years), 5 case-control studies, and 5 cross-sectional studies that were eligible for meta-analysis. Individual studies were adjusted for confounding factors such as age, sex, diabetes mellitus, and smoking. The 3 study categories were analyzed separately. Heterogeneity of the studies was assessed by Cochran Q test. The studies were homogeneous; therefore, the Mantel-Haenszel fixed-effect model was used to compute common relative risk and odds ratio (OR). Meta-analysis of the 5 prospective cohort studies (86092 patients) indicated that individuals with PD had a 1.14 times higher risk of developing CHD than the controls (relative risk 1.14, 95% CI 1.074-1.213, P < .001). The case-control studies (1423 patients) showed an even greater risk of developing CHD (OR 2.22, 95% CI 1.59-3.117, P < .001). The prevalence of CHD in the cross-sectional studies (17724 patients) was significantly greater among individuals with PD than in those without PD (OR 1.59, 95% CI 1.329-1.907, P < .001). When the relationship between number of teeth and incidence of CHD was analyzed, cohort studies showed 1.24 times increased risk (95% CI 1.14-1.36, P < .0001) of development of CHD in patients with <10 teeth. This meta-analysis indicates that both the prevalence and incidence of CHD are significantly increased in PD. Therefore, PD may be a risk factor for CHD. Prospective studies are required to prove this assumption and evaluate risk reduction with the treatment of PD.
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              Virulence factors of Porphyromonas gingivalis.


                Author and article information

                European Journal of Microbiology and Immunology
                Akadémiai Kiadó, co-published with Springer Science+Business Media B.V., Formerly Kluwer Academic Publishers B.V.
                1 September 2013
                : 3
                : 3
                : 152-162
                [ 1 ] School of Molecular Bioscience, The University of Sydney, Sydney, Australia
                [ 2 ] Institute of Dental Research, Westmead Millennium Institute and Centre for Oral Health, Westmead Hospital, Sydney, NSW, Australia
                [ 3 ] Faculty of Dentistry, The University of Sydney, Sydney, Australia
                Author notes
                [* ] (+61) 293512794, (+61) 293514726, charles.collyer@ 123456sydney.edu.au
                Original Article

                Medicine,Immunology,Health & Social care,Microbiology & Virology,Infectious disease & Microbiology
                protein structure,oral infection,gingipain adhesins, Porphyromonas gingivalis ,virulence factor


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