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Regulation of the Porphyromonas gingivalis fimA (Fimbrillin) gene.

ABSTRACT: In common with many bacterial virulence genes, the fimbrillin (fimA) gene of Porphyromonas gingivalis is modulated in response to environmental fluctuation. The trans-acting components that comprise the regulatory system for transcriptional activity of the fimA gene in P. gingivalis were investigated. Three major proteins were found to bind to the upstream region of the fimA promoter. One of these proteins was fimbrillin itself, and the other two were a major arginine protease (Rgp) and lysine protease (Kgp). Production of these proteins was necessary for maximal fimA transcription. An exogenous fimA promoter-lacZ reporter was inactive when introduced into a strain of P. gingivalis carrying a mutation in the indigenous fimA gene. Furthermore, fimA mRNA levels were significantly decreased in rgp and kgp mutant strains. These data indicate that P. gingivalis has evolved multiple levels of control of fimbrial gene expression to enhance its survival in hostile environments.

SUBMITTER: Xie H

PROVIDER: S-EPMC97752 | biostudies-literature | 2000 Dec

REPOSITORIES: biostudies-literature

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Regulation of the Porphyromonas gingivalis fimA (Fimbrillin) gene.

Xie H H Chung W O WO Park Y Y Lamont R J RJ

Infection and immunity 20001201 12

In common with many bacterial virulence genes, the fimbrillin (fimA) gene of Porphyromonas gingivalis is modulated in response to environmental fluctuation. The trans-acting components that comprise the regulatory system for transcriptional activity of the fimA gene in P. gingivalis were investigated. Three major proteins were found to bind to the upstream region of the fimA promoter. One of these proteins was fimbrillin itself, and the other two were a major arginine protease (Rgp) and lysine p ...[more]

PMID: 11083767

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Porphyromonas gingivalis FimA fimbriae: fimbrial assembly by fimA alone in the fim gene cluster and differential antigenicity among fimA genotypes.

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| S-EPMC3436787 | biostudies-literature

Distribution and molecular characterization of Porphyromonas gingivalis carrying a new type of fimA gene.

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| S-EPMC5703466 | biostudies-literature

Frequency of Porphyromonas gingivalis fimA in smokers and nonsmokers after periodontal therapy.

Project description:Porphyromonas gingivalis is one of the most important Gram-negative anaerobe bacteria involved in the pathogenesis of periodontitis. P. gingivalis has an arsenal of specialized virulence factors that contribute to its pathogenicity. Among them, fimbriae play a role in the initial attachment and organization of biofilms. Different genotypes of fimA have been related to length of fimbriae and pathogenicity of the bacterium.ObjectivesThe aim of this study was to identify 5 types of fimA genotype strains in smokers and nonsmokers with periodontitis, before and after periodontal therapy.Material and methodsThirty-one patients with periodontitis harboring P. gingivalis were selected: 16 nonsmokers (NS) and 15 smokers (SM). Clinical and microbiological parameters were evaluated at baseline and 3 months after periodontal treatment, namely: plaque index, bleeding on probe, probing depth, gingival recession and clinical attachment level. The frequency of P. gingivalis and fimA genotype strains were determined by polymerase chain reaction.ResultsType I fimA was detected in the majority of SM and NS at baseline, and the frequency did not diminish after 3 months of treatment. The frequency of type II genotype was higher in SM than NS at baseline. After 3 months, statistical reduction was observed only for types II and V fimA genotypes in SM. The highest association was found between types I and II at baseline for NS (37.5%) and SM (53.3%).ConclusionThe most prevalent P. gingivalis fimA genotypes detected in periodontal and smoker patients were genotypes I and II. However, the presence of fimA genotype II was higher in SM. Periodontal treatment was effective in controlling periodontal disease and reducing type II and V P. gingivalis fimA.

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fimA genotypes and multilocus sequence types of Porphyromonas gingivalis from patients with periodontitis.

Project description:Fimbriae are important virulence factors of pathogenic bacteria, facilitating their attachment to host and bacterial cells. In the periodontal pathogen Porphyromonas gingivalis, the fimA gene is classified into six types (genotypes I, Ib, II, III, IV, and V) on the basis of different nucleotide sequences, with fimA genotypes II and IV being prevalent in isolates from patients with periodontitis. The aims of this study were to examine the distribution of fimA genotypes in a collection of 82 P. gingivalis isolates from adult periodontitis patients of worldwide origin and to investigate the relationship between the fimA genotypes and the sequence types (STs), as determined by multilocus sequence typing (MLST), of the isolates. The fimA gene was amplified by PCR with primer sets specific for each genotype. The STs of all strains were assigned according to the MLST database for P. gingivalis (www.pubmlst.org/pgingivalis). The 82 strains showed extensive genetic diversity and were assigned to 69 STs. Only isolates with closely related STs harbored the same fimA genotype. Twenty-eight (34.1%) strains harbored fimA genotype II, while only the reference strain for fimA genotype V reacted with the primers specific for this genotype. Twenty-one isolates (25.6%) were positive by more than one of the fimA PCR assays; the most frequent combinations were genotypes I, Ib, and II (eight isolates) and genotypes I and II (four isolates). Sequencing of the fimA gene from selected isolates did not support the observed specific fimA genotype combinations, suggesting that the genotyping method used for the major fimbriae in P. gingivalis should be reevaluated.

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Potent In Vitro and In Vivo Activity of Plantibody Specific for Porphyromonas gingivalis FimA.

Project description:Fimbrial protein fimbrillin (FimA), a major structural subunit of Porphyromonas gingivalis, has been suggested as a vaccine candidate to control P. gingivalis-induced periodontal disease. Previously, cDNAs encoding IgG monoclonal antibodies (MAbs) against purified FimA from P. gingivalis 2561 have been cloned, and the MAbs have been produced in rice cell suspension. Here we examined the biological activities of the plant-produced MAb specific for FimA (anti-FimA plantibody) of P. gingivalis in vitro and in vivo. The anti-FimA plantibody recognized oligomeric/polymeric forms of native FimA in immunoblot analysis and showed high affinity for native FimA (KD = 0.11 nM). Binding of P. gingivalis (10(8) cells) to 2 mg of saliva-coated hydroxyapatite beads was reduced by 53.8% in the presence of 1 ?g/ml plantibody. Anti-FimA plantibody (10 ?g/ml) reduced invasion of periodontal ligament cells by P. gingivalis (multiplicity of infection, 100) by 68.3%. Intracellular killing of P. gingivalis opsonized with the anti-FimA plantibody by mouse macrophages was significantly increased (77.1%) compared to killing of bacterial cells with irrelevant IgG (36.7%). In a mouse subcutaneous chamber model, the number of recoverable P. gingivalis cells from the chamber fluid was significantly reduced when the numbers of bacterial cells opsonized with anti-FimA plantibody were compared with the numbers of bacterial cells with irrelevant IgG, 66.7% and 37.1%, respectively. These in vitro and in vivo effects of anti-FimA plantibody were comparable to those of the parental MAb. Further studies with P. gingivalis strains with different types of fimbriae are needed to investigate the usefulness of anti-FimA plantibody for passive immunization to control P. gingivalis-induced periodontal disease.

| S-EPMC4820508 | biostudies-literature

Proteomic peptide scan of porphyromonas gingivalis fima type ii for searching potential b-cell epitopes.

Project description:PurposeTo identify potential antigenic targets for Porphyromonas gingivalis vaccine development.Materials and methodsIn the present study, we analyzed the Porphyromonas gingivalis, fimA type II primary amino acid sequence and characterized the similarity to the human proteome at the pentapeptide level.ResultsWe found that exact peptide-peptide profiling of the fimbrial antigen versus the human proteome shows that only 19 out of 344 fimA type II pentapeptides are uniquely owned by the bacterial protein.ConclusionsThe concept that protein immunogenicity is allocated in rare peptide sequences and the search the Porphyromonas gingivalis fimA type II sequence for peptides unique to the bacterial protein and absent in the human host, might be used in new therapeutical approaches as a significant adjunct to current periodontal therapies.

| S-EPMC5159908 | biostudies-literature

The prevalence of fimA genotypes of Porphyromonas gingivalis in patients with chronic periodontitis: A meta-analysis.

Project description:FimA is an important virulence factor of Porphyromonas gingivalis (P. gingivalis). According to its DNA sequence, the fimA genotype of P. gingivalis can be divided into six categories (I, Ib, Ⅱ, III, IV, V). The fimA gene may be a key factor in the diversity of virulence found in P. gingivalis. Moreover, the role fimA plays in the pathogenesis of P. gingivalis is closely associated with periodontitis, making it an important factor of study for disease prevention and treatment. In this study, the prevalence of fimA genotypes of P. gingivalis in patients with periodontal diseases was evaluated by meta-analysis. The Embase and PubMed databases were searched for articles from 1999 to 2019 using the following search terms: Porphyromonas gingivalis or P. gingivalis; periodontitis or chronic periodontal disease; fimA or fimA genotype. The reference lists of relevant published articles were searched manually. A total of 17 studies were included in this report. A statistical software package (Stata, version 11.0/mp, StataCorp) was utilized to calculate and analyze the P. gingivalis fimA genotypes for each combined incidence estimate. The pooled rates of fimA Ⅰ, fimA Ib, fimA Ⅱ, fimA Ⅲ, fimA Ⅳ and fimA Ⅴ genotypes of P. gingivalis were 8.4% (95% CI: 5.7-11.1), 11.7% (95% CI: 7.4-16), 42.9% (95% CI: 34.2-51.7), 6.5% (95% CI: 5.1-7.9), 17.8% (95% CI: 9.0-26.5), and 3.2% (95% CI: 1.6-4.9), respectively. This study showed that the fimA Ⅱ and fimA Ⅳ genotypes of P. gingivalis are highly present in patients with periodontal disease. Therefore, these two genotypes may be related to the pathogenesis and progress of periodontal disease, one of the main risk factors of periodontitis.

| S-EPMC7592798 | biostudies-literature

<i>Porphyromonas gingivalis</i> FimA and Mfa1 fimbriae: Current insights on localization, function, biogenesis, and genotype.

Project description:In general, the periodontal pathogen Porphyromonas gingivalis expresses distinct FimA and Mfa1 fimbriae. Each of these consists of five FimA-E and five Mfa1-5 proteins encoded by the fim and mfa gene clusters, respectively. The main shaft portion comprises FimA and Mfa1, whereas FimB and Mfa2 are localized on the basal portion and function as anchors and elongation terminators. FimC-E and Mfa3-5 participate in the assembly of an accessory protein complex on the tips of each fimbria. Hence, they serve as ligands for the receptors on host cells and other oral bacterial species. The crystal structures of FimA and Mfa1 fimbrial proteins were recently elucidated and new insights into the localization, function, and biogenesis of these proteins have been reported. Several studies indicated a correlation between P. gingivalis pathogenicity and the fimA genotype but not the mfa1 genotype. We recently revealed polymorphisms of all genes in the fim and mfa gene clusters. Intriguingly, mfa5 occurred in numerous different forms and underwent duplication. Detailed structural and functional knowledge of the fimbrial proteins in the context of the entire filament could facilitate the development of innovative therapeutic strategies for structure-based drug design.

| S-EPMC8512630 | biostudies-literature

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