Frequencies of Porphyromonas gingivalis Detection in Oral-Digestive Tract Tumors.
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ABSTRACT:
SUBMITTER: Kong J
PROVIDER: S-EPMC8262194 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Porphyromonas gingivalis is an anaerobic microorganism that inhabits the oral cavity, where oxidative stress represents a constant challenge. A putative transcriptional regulator associated with oxidative stress, an oxyR homologue, is known from the P. gingivalis W83 genome sequence. We used microarrays to characterize the response of P. gingivalis to H2O2 and examine the role of oxyR in the regulation of this response. Most organisms in which oxyR has been investigated are facultative anaerobes or aerobes. In contrast to the OxyR-regulated response of these microorganisms to H2O2, the main feature of the response in P. gingivalis was a concerted up-regulation of insertion sequence elements related to IS1 transposases. Common OxyR-regulated genes such as dps and ahpFC were not positively regulated in P. gingivalis in response to H2O2. However, their expression was dependent on the presence of a functional OxyR, as revealed by microarray comparison of an oxyR mutant to the wild type. Phenotypic characterization of the oxyR mutant showed that OxyR plays a role in both the resistance to H2O2 and the aerotolerance of P. gingivalis. Escherichia coli and other bacteria with more complex respiratory requirements use OxyR for regulating resistance to H2O2 and use a separate regulator for aerotolerance. In P. gingivalis, the presence of a single protein combining the two functions might be related to the comparatively smaller genome size of this anaerobic microorganism. In conclusion, these results suggest that OxyR does not act as a sensor of H2O2 in P. gingivalis but constitutively activates transcription of oxidative-stress-related genes under anaerobic growth.
| S-EPMC1428421 | biostudies-literature
Project description:Porphyromonas gingivalis is an oral pathogen involved in the widespread disease periodontitis. In recent years, however, this bacterium has been implicated in the etiology of another common disorder, the autoimmune disease rheumatoid arthritis. Periodontitis and rheumatoid arthritis were known to correlate for decades, but only recently a possible molecular connection underlying this association has been unveiled. P. gingivalis possesses an enzyme that citrullinates certain host proteins and, potentially, elicits autoimmune antibodies against such citrullinated proteins. These autoantibodies are highly specific for rheumatoid arthritis and have been purported both as a symptom and a potential cause of the disease. The citrullinating enzyme and other major virulence factors of P. gingivalis, including some that were implicated in the etiology of rheumatoid arthritis, are targeted to the host tissue as secreted or outer-membrane-bound proteins. These targeting events play pivotal roles in the interactions between the pathogen and its human host. Accordingly, the overall protein sorting and secretion events in P. gingivalis are of prime relevance for understanding its full disease-causing potential and for developing preventive and therapeutic approaches. The aim of this review is therefore to offer a comprehensive overview of the subcellular and extracellular localization of all proteins in three reference strains and four clinical isolates of P. gingivalis, as well as the mechanisms employed to reach these destinations.
| S-EPMC6941882 | biostudies-literature
Project description:Porphyromonas gingivalis is a periodontal pathogen that resides in a complex multispecies microbial biofilm community known as dental plaque. Confocal laser scanning microscopy showed that P. gingivalis can assemble into communities in vitro with Streptococcus gordonii and Fusobacterium nucleatum, common constituents of dental plaque. Whole cell quantitative proteomics, along with mutant construction and analysis, were conducted to investigate how P. gingivalis adapts to this three species community.1156 P. gingivalis proteins were detected qualitatively during comparison of the three species model community with P. gingivalis incubated alone under the same conditions. Integration of spectral counting and summed signal intensity analyses of the dataset showed that 403 proteins were down-regulated and 89 proteins up-regulated. The proteomics results were inspected manually and an ontology analysis conducted using DAVID. Significant decreases were seen in proteins involved in cell shape and the formation of the cell envelope, as well as thiamine, cobalamin, and pyrimidine synthesis and DNA repair. An overall increase was seen in proteins involved in protein synthesis. HmuR, a TonB dependent outer membrane receptor, was up-regulated in the community and an hmuR deficient mutant was deficient in three species community formation, but was unimpaired in its ability to form mono- or dual-species biofilms.Collectively, these results indicate that P. gingivalis can assemble into a heterotypic community with F. nucleatum and S. gordonii, and that a community lifestyle provides physiologic support for P. gingivalis. Proteins such as HmuR, that are up-regulated, can be necessary for community structure.
| S-EPMC2689231 | biostudies-literature
Project description:Macrophages are phagocytic cells that play a key role in host immune response and clearance of microbial pathogens. Porphyromonas gingivalis is an oral pathogen associated with the development of periodontitis. Escape from macrophage phagocytosis was tested by infecting THP-1-derived human macrophages and RAW 264.7 mouse macrophages with strains of P. gingivalis W83 and 33277 as well as Streptococcus gordonii DL1 and Escherichia coli OP50 at MOI = 100. CFU counts for all intracellular bacteria were determined. Then, infected macrophages were cultured in media without antibiotics to allow for escape and escaping bacteria were quantified by CFU counting. P. gingivalis W83 displayed over 60% of the bacterial escape from the total amount of intracellular CFUs, significantly higher compared to all other bacteria strains. In addition, bacterial escape and re-entry were also tested and P. gingivalis W83, once again, showed the highest numbers of CFUs able to exit and re-enter macrophages. Lastly, the function of the PG0717 gene of P. gingivalis W83 was tested on escape but found not related to this activity. Altogether, our results suggest that P. gingivalis W83 is able to significantly avoid macrophage phagocytosis. We propose this ability is likely linked to the chronic nature of periodontitis.
| S-EPMC7563140 | biostudies-literature
Project description:Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.
| S-EPMC8484350 | biostudies-literature
Project description:BackgroundPorphyromonas gingivalis is part of the subgingival biofilm and a keystone species in the development of periodontitis. Interactions between P.gingivalis and other bacteria in biofilms have been shown to affect bacterial virulence. Helicobacter pylori also inhabits the subgingival biofilm, but the consequences of interactions there with P.gingivalis remain unknown. Here, we investigated how the pre-incubation of P.gingivalis with H.pylori affects P.gingivalis virulence.MethodsWe assayed P.gingivalis internalization by oral keratinocytes (OKs), hemagglutination and biofilm formation to identify alterations in virulence after pre-incubation with H. pylori. Also, we evaluated viability and migration of OKs infected with P. gingivalis, as well as the role of toll-like receptor 4 (TLR4). In addition, we quantified the mRNA of genes associated with P.gingivalis virulence.ResultsPre-incubation of P.gingivalis with H.pylori enhanced P.gingivalis biofilm formation, bacterial internalization into OKs and hemagglutination. Infection with pre-incubated P.gingivalis increased OK migration in a manner dependent on the O-antigen and linked to increased expression of the gingipain RgpB. Also, OK TLR4 participates in these events, because upon TLR4 knock-down, pre-incubated P.gingivalis no longer stimulated OK migration.DiscussionWe provide here for the first time insight to the consequences of direct interaction between P.gingivalis and H.pylori. In doing so, we shed light on the mechanism by which H. pylori presence in the oral cavity increases the severity or progression of periodontitis.
| S-EPMC9377229 | biostudies-literature
Project description:The Mfa1 fimbriae of the periodontal pathogen Porphyromonas gingivalis are involved in adhesion, including binding to synergistic species in oral biofilms. Mfa1 fimbriae are comprised of 5 proteins: the structural component Mfa1, the anchor Mfa2, and Mfa3-5 which constitute the fimbrial tip complex. Interactions among the Mfa proteins and the polymerization mechanism for Mfa1 are poorly understood. Here we show that Mfa3 can bind to Mfa1, 2, 4, and 5 in vitro, and may function as an adaptor protein interlinking other fimbrial subunits. Polymerization of Mfa1 is independent of Mfa3-5 and requires proteolytic processing mediated by the RgpA/B arginine gingipains of P. gingivalis. Both the N- and C- terminal regions of Mfa1 are necessary for polymerization; however, potential ?-strand disrupting amino acid substitutions in these regions do not impair Mfa1 polymerization. In contrast, substitution of hydrophobic amino acids with charged residues in either the N- or C- terminal domains yielded Mfa1 proteins that failed to polymerize. Collectively, these results indicate that Mfa3 serves as an adaptor protein between Mfa1 and other accessory fimbrial proteins. Mfa1 fimbrial polymerization is dependent on hydrophobicity in both the N- and C-terminal regions, indicative of an assembly mechanism involving the terminal regions forming a hydrophobic binding interface between Mfa1 subunits.
| S-EPMC5954841 | biostudies-literature
Project description:BackgroundThe Gram negative anaerobic bacterium Porphyromonas gingivalis has long been recognized as a causative agent of periodontitis. Periodontitis is a chronic infectious disease of the tooth supporting tissues eventually leading to tooth-loss. Capsular polysaccharide (CPS) of P. gingivalis has been shown to be an important virulence determinant. Seven capsular serotypes have been described. Here, we used micro-array based comparative genomic hybridization analysis (CGH) to analyze a representative of each of the capsular serotypes and a non-encapsulated strain against the highly virulent and sequenced W83 strain. We defined absent calls using Arabidopsis thaliana negative control probes, with the aim to distinguish between aberrations due to mutations and gene gain/loss.ResultsOur analyses allowed us to call aberrant genes, absent genes and divergent regions in each of the test strains. A conserved core P. gingivalis genome was described, which consists of 80% of the analyzed genes from the sequenced W83 strain. The percentage of aberrant genes between the test strains and control strain W83 was 8.2% to 13.7%. Among the aberrant genes many CPS biosynthesis genes were found. Most other virulence related genes could be found in the conserved core genome. Comparing highly virulent strains with less virulent strains indicates that hmuS, a putative CobN/Mg chelatase involved in heme uptake, may be a more relevant virulence determinant than previously expected. Furthermore, the description of the 39 W83-specific genes could give more insight in why this strain is more virulent than others.ConclusionAnalyses of the genetic content of the P. gingivalis capsular serotypes allowed the description of a P. gingivalis core genome. The high resolution data from three types of analysis of triplicate hybridization experiments may explain the higher divergence between P. gingivalis strains than previously recognized.
| S-EPMC2955634 | biostudies-literature
Project description:Oral mucosa provides the first line of defense against a diverse array of environmental and microbial irritants by forming the barrier of epithelial cells interconnected by multiprotein tight junctions (TJ), adherens junctions, desmosomes, and gap junction complexes. Grainyhead-like 2 (GRHL2), an epithelial-specific transcription factor, may play a role in the formation of the mucosal epithelial barrier, as it regulates the expression of the junction proteins. The current study investigated the role of GRHL2 in the Porphyromonas gingivalis (Pg)-induced impairment of epithelial barrier functions. Exposure of human oral keratinocytes (HOK-16B and OKF6 cells) to Pg or Pg-derived lipopolysaccharides (Pg LPSs) led to rapid loss of endogenous GRHL2 and the junction proteins (e.g., zonula occludens, E-cadherin, claudins, and occludin). GRHL2 directly regulated the expression levels of the junction proteins and the epithelial permeability for small molecules (e.g., dextrans and Pg bacteria). To explore the functional role of GRHL2 in oral mucosal barrier, we used a Grhl2 conditional knockout (KO) mouse model, which allows for epithelial tissue-specific Grhl2 KO in an inducible manner. Grhl2 KO impaired the expression of the junction proteins at the junctional epithelium and increased the alveolar bone loss in the ligature-induced periodontitis model. Fluorescence in situ hybridization revealed increased epithelial penetration of oral bacteria in Grhl2 KO mice compared with the wild-type mice. Also, blood loadings of oral bacteria (e.g., Bacteroides, Bacillus, Firmicutes, β-proteobacteria, and Spirochetes) were significantly elevated in Grhl2 KO mice compared to the wild-type littermates. These data indicate that Pg bacteria may enhance paracellular penetration through oral mucosa in part by targeting the expression of GRHL2 in the oral epithelial cells, which then impairs the epithelial barrier by inhibition of junction protein expression, resulting in increased alveolar tissue destruction and systemic bacteremia.
| S-EPMC6704429 | biostudies-literature
Project description:Mechanisms by which Porphyromonas gingivalis (P. gingivalis) infection enhances oral tumor growth or resistance to cell death remain elusive. Here, we determined that P. gingivalis infection mediates therapeutic resistance via inhibiting lethal mitophagy in cancer cells and tumors. Mechanistically, P. gingivalis targets the LC3B-ceramide complex by associating with LC3B via bacterial major fimbriae (FimA) protein, preventing ceramide-dependent mitophagy in response to various therapeutic agents. Moreover, ceramide-mediated mitophagy is induced by Annexin A2 (ANXA2)-ceramide association, involving the E142 residue of ANXA2. Inhibition of ANXA2-ceramide-LC3B complex formation by wild-type P. gingivalis prevented ceramide-dependent mitophagy. Moreover, a FimA-deletion mutant P. gingivalis variant had no inhibitory effects on ceramide-dependent mitophagy. Further, 16S rRNA sequencing of oral tumors indicated that P. gingivalis infection altered the microbiome of the tumor macroenvironment in response to ceramide analog treatment in mice. Thus, these data provide a mechanism describing the pro-survival roles of P. gingivalis in oral tumors.
2024-06-23 | PXD051568 | Pride