Characterization of a bacterial tyrosine kinase in Porphyromonas gingivalis involved in polymicrobial synergy
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ABSTRACT:
ORGANISM(S): Porphyromonas gingivalis ATCC 33277
SUBMITTER: David Beck
PROVIDER: E-GEOD-55192 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:Porphyromonas gingivalis, the keystone pathogen responsible for dysbiosis in the oral microbiome, the development of periodontal diseases, and the contribution to systemic comorbidities, is a heme auxotroph. It encodes only four enzymes in the heme biosynthesis pathway, namely HemD, HemN, HemG, and HemH. HemH protein is a ferrochelatase involved in the final step of heme biosynthesis by inserting iron ions (Fe2+) into protoporphyrin IX. This study aimed to analyze the effect of hemH gene deletion on P. gingivalis gene expression, thereby verifying its importance for P. gingivalis.
2026-03-03 | E-MTAB-16130 | biostudies-arrayexpress
Project description:Porphyromonas gingivalis is a keystone pathogen responsible for oral microbiome dysbiosis, the development of periodontal disease, and may be involved in the development of systemic comorbidities. As a heme auxotroph, P. gingivalis relies on host hemoproteins as its primary sources of heme and iron. Although heme acquisition in P. gingivalis is relatively well characterized, considerably less is known about its pathways for iron uptake and the regulation of iron and heme homeostasis. P. gingivalis encodes four enzymes associated with the heme biosynthesis pathway, namely HemD, HemN, HemG, and HemH. HemH is a ferrochelatase responsible for the final step of heme biosynthesis, catalyzing the insertion of ferrous iron (Fe²⁺) into protoporphyrin IX. In addition, P. gingivalis expresses the Iht system, which plays a role in iron/heme utilization. One of its components, IhtB, is a heme-binding protein homologous to CbiK cobaltochelatases. Based on this homology, IhtB is hypothesized to function as a reverse ferrochelatase, facilitating the removal of iron from heme and thereby contributing to iron acquisition. This study aimed to investigate the effect of ihtB and hemH gene deletions on P. gingivalis gene expression under heme- and iron-replete conditions, to elucidate the roles of IhtB and HemH chelatases in heme and iron homeostasis.
2026-03-03 | E-MTAB-16135 | biostudies-arrayexpress
Project description:Porphyromonas gingivalis is considered a keystone pathogen responsible for dysbiosis in the oral microbiome, leading to the development of periodontal disease and contributing to various systemic comorbidities. Although P. gingivalis requires heme for growth and virulence, it is unable to synthesize heme de novo and therefore relies on host hemoproteins as its source. To acquire heme, the bacterium utilizes the Hmu system, which is composed of six proteins (HmuYRSTUV). HmuY functions as a hemophore-like protein that sequesters heme from host hemoproteins; HmuR serves as an outer membrane receptor responsible for heme uptake. The remaining four proteins (HmuS, HmuT, HmuU, and HmuV) are uncharacterized. HmuS has been proposed to act as a reverse ferrochelatase, due to its homology with CobN cobaltochelatases; therefore, it could catalyze the removal of iron from heme. The released iron could then be transported into the cytoplasm via the HmuTUV proteins. However, the specific role of HmuS in P. gingivalis has never been studied or confirmed. Therefore, this study aimed to investigate the effect of hmuS gene deletion on global gene expression in P. gingivalis, thereby assessing its role in iron acquisition and overall bacterial fitness.
2026-04-24 | E-MTAB-16197 | biostudies-arrayexpress
Project description:Porphyromonas gingivalis plays a key role in periodontal disease and has been associated with several serious systemic diseases. Its fimbriae are a major virulence factor. We re-cently demonstrated the formation of bundles of long FimA fimbriae in strain ATCC 33277. Transmission (TEM) and scanning electron microscopy (SEM) were used to exam-ine a collection of P. gingivalis strains representing all seven known FimA genotypes (I, Ib, IIa, IIb, III–V) and a P. gulae strain (type A). Additionally, two P. gingivalis strains (ATCC 49417 and 84Pg1) were investigated in dual species approaches with Fusobacterium nucle-atum, Streptococcus oralis, and human gingival fibroblasts. To evaluate a suspected connec-tion with the fimbriae accessory proteins FimCDE, proteomic analysis of outer membrane vesicles (OMVs) was performed. Bundling was confirmed to occur regardless of FimA genotype but is impaired by strong capsule formation. For the first time fimbri-ae-associated OMVs (FAVs) were observed. Tubular and chain-like extensions of the outer membrane (OMEs) were identified in most strains examined, including P. gulae. Bundled fimbriae, FAVs, and OMEs were further suggested to connect to F. nucleatum and S. oralis. Proteome analysis revealed ratios of FimA to accessory proteins to be approximately 13:1 for FimC and FimD and approximately 7:1 for FimE. The results imply more accessory proteins per fimbriae or short FimA fimbriae in OMVs. Since FimCDE is known to be re-sponsible for the adhesion properties and autoaggregation of FimA fimbriae, we propose that it could also mediate the stability of bundled fimbriae and the binding of OMVs to (bundled) fimbriae.
2025-12-30 | PXD070506 | Pride
Project description:The oral periodontal pathogen Porphyromonas gingivalis must adapt to ever changing environment to survive and cause disease. So far most of the efforts concerning the regulatory mechanisms employed by the bacterium centered on DNA-binding regulators. Here we focused on a RNA-binding protein that is indispensable for the bacterium to survive with host cells. We have determined the proteome affected by deletion of the protein, designated here PgRBP1. Three strains were used: WT, PgRBP1-deficient strain designated V3139 and a complemented strain V3236. In total, 1,393 proteins were identified. 592 proteins in the comparison of P. gingivalis 3139 vs. WT, 228 proteins in the comparison of P. gingivalis 3236 vs. WT, and 276 proteins in the comparison of P. gingivalis 3139 vs. 3236 showed differential level with statistical significance
2025-06-02 | PXD034144 | Pride
Project description:High-density tiling microarray and RNA sequencing technologies were used to analyze the transcriptome of Porphyromonas gingivalis. The compiled P. gingivalis transcriptome were based on total RNA samples isolated from three different laboratory culturing conditions and the strand-specific transcription profiles generated covered the entire genome including both protein coding and non-coding regions. The transcription profiles revealed various operon structures, 5' and 3' end untranslated regions (UTRs), differential expression patterns, and several not-yet annotated transcripts within intergenic and antisense regions. Further transcriptome analysis identified the majority of the genes to be expressed within operons and most 5' and 3' ends to be protruding UTRs of which several 3M-CM-"M-BM-^@M-BM-^Y UTRs were extended to overlap genes encoded on the opposite/antisense strand. Extensive antisense RNAs were identified opposite to most of insertion sequence (IS) elements. With the growing realization that non-coding RNAs play important biological functions, the comprehensive transcriptome profiles compiled in this study are of great value for the further understanding of gene regulation and virulence mechanism in this periodontal pathogen. The transcriptome profiles can be viewed at and downloaded from the 'Microbial Transcriptome Database' web site http://bioinformatics.forsyth.org/mtd. 3 total RNA samples from growing P. gingivalis strain W83 under different media conditions subjected to RNA-Seq.
2011-10-01 | E-GEOD-30452 | biostudies-arrayexpress
Project description:Porphyromonas gingivalis is a keystone periodontal pathogen implicated in a variety of diseases ranging from periodontitis to Alzheimer’s disease. A hallmark of P. gingivalis is the constitutive production of a peptidyl-arginine deiminase (PPAD), which converts positively charged arginine residues into charge-neutral citrulline residues. The PPAD enzyme is known to be localized to the bacterial outer membrane and outer membrane vesicles (OMVs). Our present study was aimed at dissecting the roles of PPAD in the bacterial evasion of human macrophages and passage of cellular barriers. Here, we show that PPAD is required for activity of the arginine-specific proteases RgpA and RgpB, which are critical virulence factors of P. gingivalis. Furthermore, we show that the absence of PPAD leads to an increased OMV charge. Both changes impact the immune evasion strategy of P. gingivalis, as the PPAD-deficient bacteria display increased biofilm formation while their ability to evade and kill human macrophages is strongly reduced. In fact, PPAD-deficient bacteria and OMVs are more effectively internalized by macrophages and they elicit altered inflammatory macrophage responses, as demonstrated by reduced secretion of pro-inflammatory cytokines and major changes in the macrophage proteome. Intriguingly, we show that P. gingivalis OMVs have a high propensity for in vitro blood-brain barrier passage through transcytosis, which is significantly increased by PPAD-deficiency. This implies that OMV citrullination is a critical determinant for trafficking of P. gingivalis-derived vesicles within the human host. Altogether, our present findings explain how PPAD shapes the immunomodulatory and invasive properties of P. gingivalis and its OMVs.
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Project description:RNA-Seq of wild-type Porphyromonas gingivalis compared to ΔPGN_1524 mutant
2014-07-19 | GSE55192 | GEO
Project description:This project investigated the phenotypic characteristics of Metronidazole-tolerant Porphyromonas gingivalis persisters, the relevant modulatory effects of hemin and their underlying survival mechanisms. Proteomic analysis was performed to delineate the protein expression profiles of Metronidazole-tolerant P. gingivalis persister fractions and the controls incubated with different levels of hemin supplementation.
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Project description:We report the study of the mechanism of action of Porphyromonas gingivalis on human oral epithelial cells based on high-throughput sequencing technology. By acting Porphyromonas gingivalis and its metabolites on human oral epithelial cells separately, the mechanism of Porphyromonas gingivalis evading immune surveillance and causing local and deep tissue diffusion to induce systemic diseases was studied. This study provides a framework for studying the pathogenic mechanism of Porphyromonas gingivalis.
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