Colin G Hawkes, Travis J Chiarelli, Doaa N Abdallah, Grayson Way, Huiping Zhou, Jason A Carlyon, Daniel P Miller
{"title":"The Outcome of Intracellular Selenomonas sputigena and its Impact on Gingival Keratinocytes.","authors":"Colin G Hawkes, Travis J Chiarelli, Doaa N Abdallah, Grayson Way, Huiping Zhou, Jason A Carlyon, Daniel P Miller","doi":"10.1111/omi.70021","DOIUrl":"10.1111/omi.70021","url":null,"abstract":"<p><p>Selenomonas sputigena is an understudied oral pathobiont associated with periodontitis and dental caries. We recently demonstrated that S. sputigena binds to gingival epithelial cells (GECs), where afterwards the bacterium causes robust in vitro pro-inflammatory cytokine production and migration of monocytes and neutrophils. Here, we report that extracellular adherent S. sputigena are subsequently internalized by GECs. Fluorescently labeled intracellular S. sputigena were observed in two gingival keratinocyte cell lines and primary cells. Oxygen-killed S. sputigena was found within GECs at a similar rate to living bacteria, suggesting active protein synthesis is not required for internalization. Host-cell actin polymerization was essential for the internalization of S. sputigena. Electron microscopy revealed that intracellular S. sputigena is located within a single membrane vesicle tightly wrapped around the bacterium which is decorated with LAMP1, indicating that S. sputigena is ultimately trafficked to a lysosome-like vesicle. Although S. sputigena mRNA was detectable within GECs, it rapidly decreased by 24 h post-inoculation. This differed from bacterial morphology, which remained intact up to 48 h. Induction of CXCL8 expression was concurrent with intracellular S. sputigena morphological integrity, suggesting that, while the bacteria are likely dead, bacterial macromolecules perpetuate inflammation in GECs. Collectively, this study demonstrates S. sputigena can be taken into gingival keratinocytes, where the bacterium induces inflammatory responses, but S. sputigena is ultimately processed by lysosomal machinery and is cleared from the intracellular niche in GECs.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"131-144"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Random Mutagenesis in Porphyromonas gingivalis Enables Isolation of Mutants With Enhanced Secreted Protease Activity.","authors":"Takeru Nakabayashi, Satoshi Yuhara, Kosei Tanaka","doi":"10.1111/omi.70024","DOIUrl":"10.1111/omi.70024","url":null,"abstract":"<p><p>Porphyromonas gingivalis is a key pathogen in periodontitis, with secreted proteases as major virulence factors. We developed a screening method to generate and identify P. gingivalis mutants with elevated protease activity. Mutations were induced using the mutagens 2,6-diaminopurine (2,6-DAP) or ethyl methanesulfonate (EMS), and the mutagenized cells were subsequently plated on casein agar. During colony growth, the medium became opaque due to partial casein precipitation, whereas colonies with higher protease activity produced clear halos through casein degradation. Colonies that formed halos earlier than the wild type were selected for further analysis. Liquid culture assays of the supernatants identified four strains with enhanced protease activity, of which two were 2,6-DAP-derived and two were EMS-derived. Whole-genome sequencing revealed that the two 2,6-DAP-derived strains carried mutations in iron transport-related genes (foeA and tonB, respectively), likely increasing protease levels through iron limitation-induced upregulation of rgpA. The two EMS-derived strains contained multiple mutations, including one in rgpA, a major protease gene. The N-terminal region of RgpA, which contains the protease motif, harbored the G450D mutation in one strain and the C600Y mutation in the other. These results demonstrate that our method efficiently generates P. gingivalis mutants with protease gene alterations that increase enzymatic activity. This approach provides a useful tool for studying protease function and virulence mechanisms in this pathogen, and for identifying genes that affect protease secretion.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"158-164"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yujie Zhang, Zhanyi Chen, Meiling Jing, Zhengwei Huang, Mengying Mao
{"title":"Streptococcus mutans CcpA Promotes Biofilm Exopolysaccharide Production and Virulence Gene Expression.","authors":"Yujie Zhang, Zhanyi Chen, Meiling Jing, Zhengwei Huang, Mengying Mao","doi":"10.1111/omi.70027","DOIUrl":"10.1111/omi.70027","url":null,"abstract":"<p><p>Streptococcus mutans is a key cariogenic pathogen of dental caries due to its strong ability to synthesize extracellular glucans and form biofilms. Glucosyltransferases, encoded by gtfB/C/D genes in S. mutans, are responsible for producing biofilm exopolysaccharides (EPS) and are considered to be critical virulence factors. Previous studies have highlighted the roles of various regulatory factors of gtf genes in S. mutans. Here, we investigated the role of the global transcriptional regulator CcpA encoded by ccpA in regulating the EPS synthesis and biofilm formation of S. mutans. A ccpA in-frame deletion strain was observed to develop shiny, round colonies and longer cell length. In addition, the deletion of ccpA resulted in impaired growth, diminished synthesis of EPS, and reduced biofilm formation. Transcriptome analysis revealed that differentially expressed genes in the ccpA deletion strain were significantly enriched in pathways of carbohydrate transport and metabolism, in which the expressions of gtfB and gtfC were downregulated markedly. Electrophoretic mobility shift assays confirmed that CcpA directly binds to the promoter sequences of gtfB and gtfC, with a higher affinity for gtfC. Moreover, the expression level of ccpA in part explained differences in the ability to synthesize sufficient EPS and form stable biofilm in clinically isolated strains. These findings highlight that CcpA plays a crucial role in the EPS production and biofilm formation of S. mutans through directly binding to the promoter regions of gtfB and gtfC. This study provides novel insights into the pathogenic mechanisms of S. mutans and potential strategies for the prevention and treatment of dental caries.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"165-178"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ali A Abdulkareem, Sarhang S Gul, Hayder R Abdulbaqi, Aram M Sha, Philip M Preshaw
{"title":"Assessing Evidence to Include Filifactor alocis as a Novel Candidate in Socransky's Complexes.","authors":"Ali A Abdulkareem, Sarhang S Gul, Hayder R Abdulbaqi, Aram M Sha, Philip M Preshaw","doi":"10.1111/omi.70018","DOIUrl":"10.1111/omi.70018","url":null,"abstract":"<p><p>Socransky's complexes have identified a range of bacteria as key contributors to the onset and progression of periodontal disease. However, advancements in microbiological detection methods have allowed for exploration of the microbiome in periodontal health/disease in greater detail. In recent years, Filifactor alocis has emerged as a potential periodontal pathogen. Therefore, the aim of this review was to investigate whether this bacterium could be included in Socransky's model by summarizing the available evidence. A comprehensive literature search performed using PubMed, ScienceDirect, and Scopus databases was undertaken. The retrieved articles were filtered according to defined eligibility criteria, which yielded 24 studies. Data were extracted from these observational and clinical studies to synthesize findings. Findings regarding the host immune response were derived from in vitro and experimental animal models and narratively summarized. Observational studies and clinical trials showed heterogeneity and a lack of standardized outcomes. However, the general trend indicated a higher prevalence of F. alocis at diseased sites than at healthy sites. In addition, periodontal treatment was found to significantly reduce F. alocis levels and was associated with improvements in clinical periodontal parameters. Experimental models and in vitro studies showed that F. alocis exhibits a range of virulence attributes and pathogenic behavior similar to that of putative pathogenic periodontal bacteria. The evidence is not sufficient to include F. alocis as a new member of Socransky's model. However, this review suggests that this bacterium has the potential to be included in Socransky's complexes in the future after further research which would require to be highly standardized to enhance comparability and generalizability of findings.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"117-130"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145970943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Taylor C Boone, Swetha K Shankar, Melodie L Weller
{"title":"Environmental Stress Induces Altered Composition of Streptococcus mutans Membrane Vesicles: pH-Driven Changes in Membrane Vesicle Production and Composition.","authors":"Taylor C Boone, Swetha K Shankar, Melodie L Weller","doi":"10.1111/omi.70022","DOIUrl":"10.1111/omi.70022","url":null,"abstract":"<p><p>Bacteria produce membrane vesicles (MVs) in response to environmental stress and genetic changes. Previous studies have shown that MVs can trigger inflammatory responses and may serve as important mediators of host-microbe interactions. Given the dynamic nature of the oral microbiome, bacteria such as Streptococcus mutans are frequently exposed to environmental fluctuations that could alter MV production. The objective of this study was to investigate whether inducing stress conditions would affect MV production and morphology in S. mutans, a prominent oral pathogen. Cultures were subjected to different pH conditions to mimic environmentally relevant stress. MVs were isolated and purified in order to characterize and assess changes in yield, size, and cargo. Our findings show that acidic stress significantly increased MV production while reducing average MV size. We also observed significant differences in MV content when compared to control conditions. These changes may reflect bacterial adaptation strategies and could influence how MVs interact with host immune systems. Overall, this study highlights the potential for environmental stress to reshape MV-mediated communication in the oral microbiome and provides a foundation for exploring how such changes may contribute to inflammation and oral disease.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"145-157"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13121933/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bin Zhang, Shihao Hou, Anqi Zhang, Jielin Yang, Wenjiao Zhang, Shijie Zhu, Hong Chen, Ruizhe Huang
{"title":"GcrR in Streptococcus mutans Inhibits the Morphological Transition of Candida albicans Through Ras1-cAMP/PKA Pathway in the Cross-Kingdom Biofilms.","authors":"Bin Zhang, Shihao Hou, Anqi Zhang, Jielin Yang, Wenjiao Zhang, Shijie Zhu, Hong Chen, Ruizhe Huang","doi":"10.1111/omi.70026","DOIUrl":"https://doi.org/10.1111/omi.70026","url":null,"abstract":"<p><p>The dual-species biofilms formed by Streptococcus mutans and Candida albicans exhibit enhanced cariogenic potential due to the production of extracellular polysaccharides (EPSs). The response regulator GcrR in S. mutans negatively regulates EPS synthesis, but its impact on dual-species biofilms remains unclear. The objective of the present study was to investigate the effect of GcrR on the cariogenicity of cross-kingdom biofilms established by S. mutans and C. albicans. The crystal violet (CV) staining was conducted to evaluate the dual-species biofilm formation. The anthrone-sulfuric acid assay was employed to assess EPS formation. The biofilm morphology was visualized through scanning electron microscopy (SEM), and the structure was examined by confocal laser scanning microscopy (CLSM). The expression levels of genes were determined by quantitative real-time PCR (qRT-PCR). The animal assay was conducted to elucidate the anti-cariogenic effect of GcrR. The overexpression of GcrR suppressed dual-species biofilm formation, which was accompanied by a reduction in both water-soluble glucans (WSGs) and water-insoluble glucans (WIGs). The morphological transformation of C. albicans from yeast to hyphal form was inhibited by GcrR. Expression of gtfB/D and gbpB/C genes in S. mutans and Ras1-cAMP/PKA pathway genes in C. albicans was downregulated. Furthermore, we found that GcrR attenuated the virulence of dual-species biofilms. This study suggests that GcrR in S. mutans plays a critical role in modulating the cariogenic potential of bacterial-fungal biofilms.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sara E Edmonds, Hernan Grenett, Priscilla Grenett, Jessica A Scoffield
{"title":"The ComEA/ComEC Operon is Critical for Nitrosative Stress Tolerance by an Oral Commensal.","authors":"Sara E Edmonds, Hernan Grenett, Priscilla Grenett, Jessica A Scoffield","doi":"10.1111/omi.70032","DOIUrl":"https://doi.org/10.1111/omi.70032","url":null,"abstract":"<p><p>Oral commensal streptococci play a large role in mediating microbial homeostasis. Our prior work has demonstrated that hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) produced by oral commensal streptococci can react with salivary nitrite (NO<sub>2</sub>) and generate peroxynitrite (ONOO<sup>-</sup>), a potent antimicrobial. We have shown that the combinatorial antimicrobial effects of NO<sub>2</sub> and H<sub>2</sub>O<sub>2</sub> produced from the commensal Streptococcus parasanguinis inhibit the colonization and pathogenesis of oral pathogens to promote homeostasis. Remarkably, S. parasanguinis is highly resistant to NO<sub>2</sub> and ONOO<sup>-</sup>. However, it remains unclear how S. parasanguinis tolerates nitrosative stress. The goal of this study was to identify mechanisms used by S. parasanguinis to resist NO<sub>2</sub>-mediated nitrosative stress. Transcriptomics analysis revealed that the DNA uptake gene, comEA was upregulated during growth on 2 mM NaNO<sub>2</sub>. Further, loss of the ComEA/ComEC DNA uptake locus resulted in increased sensitivity to peroxynitrite and a decrease in biofilm development, intracellular nitrite transport, H<sub>2</sub>O<sub>2</sub> production, and was defective for colonization in a Drosophila melanogaster colonization model. In summary, our data show that the ComEA/EC DNA uptake operon is critical for key aspects of S. parasanguinis physiology and potentially impacts S. parasanguinis's ability to colonize and modulate homeostasis in the oral cavity.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chiaki Yamada, Gang Peng, James A Johnson, Amilia Nusbaum, Natasha Sanz, Hawra AlQallaf, Frank Nichols, Alexandru Movila
{"title":"Porphyromonas gingivalis-Derived Virulence Lipids Accelerate Osteoclastogenesis Independently of High Mobility Group Box Protein-1 Canonical Signaling.","authors":"Chiaki Yamada, Gang Peng, James A Johnson, Amilia Nusbaum, Natasha Sanz, Hawra AlQallaf, Frank Nichols, Alexandru Movila","doi":"10.1111/omi.70015","DOIUrl":"10.1111/omi.70015","url":null,"abstract":"<p><p>Periodontal bacterial pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) accelerate inflammatory osteoclastogenesis, resulting in alveolar bone loss. The core PAMP and DAMP prototype molecules are periodontal bacterium Porphyromonas gingivalis-derived virulence lipids, for example, phosphoglycerol dihydroceramide (PGDHC) and lipopolysaccharide (LPS Pg), and the host non-histone alarmin high mobility group box protein-1 (HMGB1), respectively. Although it was reported that extracellularly released HMGB1 is critical for the promotion of sepsis inflammation in response to non-periodontal bacterial LPS, our understanding of the crosstalk between HMGB1 and P. gingivalis-derived virulence lipids remains limited. Therefore, we used Hmgb1<sup>fl/fl</sup> LysM-Cre<sup>+</sup> mice with ablated HMGB1 mRNA and littermate Hmgb1<sup>fl/fl</sup> LysM-Cre<sup>-</sup> controls. We observed limited Hmgb1<sup>fl/fl</sup> LysM-Cre<sup>+</sup> osteoclastogenesis compared to Hmgb1<sup>fl/fl</sup> in response to RANKL in vitro. Furthermore, recombinant HMGB1 protein restored osteoclast formation in Hmgb1<sup>fl/fl</sup> LysM-Cre<sup>+</sup> cells, indicating the pivotal role of extracellular HMGB1 in osteoclastogenesis in vitro. Using bulk RNA-sequencing, we identified the diminished osteoclastogenesis in Hmgb1<sup>fl/fl</sup> LysM-Cre<sup>+</sup> cells are linked to accelerated expression of canonical osteoclast-suppressing interferon genes. We surprisingly detected that PGDHC and LPS Pg accelerate osteoclastogenesis in Hmgb1<sup>fl/fl</sup> LysM-Cre<sup>+</sup> cells in vitro. Using bulk RNA-sequencing and real-time PCR assays, we confirmed that PGDHC diminishes the expression patterns of different interferon-inducible guanylate-binding proteins (GBP 3, 4, 5, 9). At the same time, LPS Pg accelerates the expression of osteoclast-promoting matrix metalloproteases (MMP 8 and 12) mRNAs. The results suggest that the RANKL-primed osteoclastogenesis accelerated by P. gingivalis-derived virulence lipids is mediated by different MMP or GBP signaling pathways independently from canonical HMGB1 signaling.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"85-93"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12964516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional Analysis of Treponema denticola Periplasmic Flagella: Roles of FlaB1, FlaB2, and FlaB3 in Morphology and Motility.","authors":"Chen-Hsuan Chiu, Mari Fujita, Keiji Nagano","doi":"10.1111/omi.70020","DOIUrl":"10.1111/omi.70020","url":null,"abstract":"<p><p>Treponema denticola is a Gram-negative, anaerobic spirochete associated with periodontal disease. It navigates highly viscous environments using periplasmic flagella located between the inner and outer membranes. The flagellum is composed of three homologous flagellin proteins-FlaB1, FlaB2, and FlaB3-encoded by the flaB1, flaB2, and flaB3 genes, respectively, and is enwrapped by the sheath protein FlaA, encoded by the flaA gene. To investigate the roles of the three FlaB flagellins in cell morphology and motility, we constructed mutants lacking different combinations of the flaB genes, including double and triple deletions. The deletion of one or two flaB genes did not affect the transcription or protein expression of the remaining flaB gene(s). Normal flagellar filaments were observed when at least one FlaB was expressed but were absent in the complete flaB deletion mutant, which also exhibited an elongated cell shape. The flagella had no significant impact on bacterial growth. In liquid medium, most mutants exhibited rotational movement comparable to the parent strain, although some showed an increased population of cells with higher rotation rates. However, in a medium containing 0.5% agar, deletion of any two or three flaB genes significantly reduced motility. These findings suggest that the expression of at least two FlaB flagellins is required for the potent movement of T. denticola.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"107-114"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ayu Takai, Kaya Yoshida, Yuka Hiroshima, Ayu Ikuta, Mariko Seyama, Yuta Uemura, Hiromichi Yumoto, Kazumi Ozaki
{"title":"Porphyromonas gingivalis Outer Membrane Vesicles-Associated DNA Triggers Inflammation by Inducing IL-6 in Astrocytes.","authors":"Ayu Takai, Kaya Yoshida, Yuka Hiroshima, Ayu Ikuta, Mariko Seyama, Yuta Uemura, Hiromichi Yumoto, Kazumi Ozaki","doi":"10.1111/omi.70030","DOIUrl":"https://doi.org/10.1111/omi.70030","url":null,"abstract":"<p><p>Porphyromonas gingivalis (Pg), a key pathogen in periodontal disease, is suggested to be involved in the progression of Alzheimer's disease (AD); however, the molecular mechanism remains unclear. We previously reported that Pg-released outer membrane vesicles (OMVs) were detected in the brains of mice after intraperitoneal administration. We here investigated the effects of Pg OMVs on astrocytes, the most abundant glial cells in the central nervous system, which are involved in neuroinflammation. We demonstrated that Pg OMVs increased the expression of interleukin-6 (IL-6) mRNA, which is associated with the pathogenesis of AD, in a Toll-like receptor (TLR)2/4-independent manner in human astrocyte SVG p12 cells. Whole-genome sequencing revealed that Pg OMVs contained Pg genomic DNA, which was critical for IL-6 mRNA induction. The tracking of fluorescent-labeled Pg OMV-associated DNA revealed that Pg OMVs were transported into SVG p12 cells. Endocytosis inhibitors attenuated IL-6 mRNA expression induced by Pg OMVs, suggesting that the incorporation of Pg OMVs by endocytosis is important for IL-6 mRNA induction. Furthermore, the incorporated Pg OMV-associated DNA increased IL-6 mRNA expression via the TLR9 pathway. Our study advances understanding of the role of Pg OMVs, which may contribute to the onset and progression of AD in periodontal disease.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}