Molecular Oral Microbiology最新文献

{"title":"Fretibacterium: Exploring Its Pathogenic Potential in Oral Infectious Diseases.","authors":"Lisha Liang, Pengbo Liu, Dongzhe Song","doi":"10.1111/omi.70004","DOIUrl":"10.1111/omi.70004","url":null,"abstract":"<p><p>Oral infectious diseases, particularly inflammatory periodontal lesions, exert a substantial impact on healthcare systems and economies, as acknowledged by the World Health Organization. The prevailing consensus attributes the onset of oral infectious diseases to dysbiosis within the intricate oral microbiome. In this context, Fretibacterium-a strictly anaerobic genus whose representative species, Fretibacterium fastidiosum, was classified in 2013 as the third human oral species within the Synergistetes phylum-has garnered attention for its progressive enrichment in periodontitis and distinct abundance profiles in health versus disease. This review synthesizes current knowledge on Fretibacterium's role in periodontal disease, dental caries, endodontic infections, and peri-implantitis, with emphasis on its virulence mechanisms. Then further explore its clinical associations with systemic conditions (e.g., diabetes) and evaluate conventional and emerging therapeutic strategies. By providing evidence-based insights, this work aims to guide clinical management and future research directions.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"235-242"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883204","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}

{"title":"Systematic Analysis of Lysine Succinylation in Streptococcus mutans.","authors":"Ting Tong, Ziyi Yang, Xiaoqiong Li, Qizhao Ma, Tao Gong, Dian Zhang, Jumei Zeng, Yuqing Li","doi":"10.1111/omi.70007","DOIUrl":"10.1111/omi.70007","url":null,"abstract":"<p><p>Lysine succinylation (Ksuc) is a novel post-translational modification (PTM), which regulates biological functions in bacteria. Streptococcus mutans has been identified as a predominant cariogenic pathogen responsible for the initiation and progression of dental caries. However, lysine succinylation in S. mutans has not yet been investigated. In this study, a global lysine succinylome was analyzed to examine Ksuc in S. mutans. Overall, 2250 succinylated sites in 580 proteins were identified. Quantitative analysis demonstrated that Ksuc substrates were substantially altered in the biofilm growth state compared with the planktonic growth state. These differentially succinylated proteins were distributed across various cellular components and involved in crucial biological pathways, including translation, ribosomal structure, and biogenesis. Furthermore, lysine acetylation and succinylation extensively overlapped in S. mutans, and these bimodified proteins were associated with biofilm formation, glycolysis, and pyruvate metabolism. These results provided a foundation to further investigate the role of Ksuc in S. mutans pathogenicity and expand our understanding of Ksuc functions in bacterial physiology and virulence.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"278-288"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961761","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}

{"title":"Transcriptional Regulon Controlled by Tyrosine Phosphatases in Porphyromonas gingivalis.","authors":"Gatphan Atassi, Kendall S Stocke, Richard J Lamont","doi":"10.1111/omi.70003","DOIUrl":"10.1111/omi.70003","url":null,"abstract":"<p><p>Tyrosine phosphorylation/dephosphorylation post-translational modification (PTM) of proteins in bacteria can control their function and location. PTM of transcriptional regulators and DNA-binding proteins, as well as components of their signaling pathways, can impact gene expression. However, little is known regarding the global impact of tyrosine phosphatases on the bacterial transcriptome. In this study, we performed RNA-Seq of Porphyromonas gingivalis wild type (WT) along with strains Δltp1 and Δphp1 with mutations in the genes encoding the two major tyrosine phosphatases, Ltp1 and Php1, respectively. Moreover, these strains were tested in vitro and in vivo (mouse abscess) conditions. Both the Δltp1 and the Δphp1 mutants exhibited little transcriptional difference to the parental strain when cultured in vitro. In vivo, comparison of the Δphp1 mutant to the WT showed a number of differentially regulated genes (DEGs) associated with transporter systems. In vivo DEGs in Δltp1 included one of the efflux ABC transporter systems also regulated in the Δphp1 mutant; however, the primary biological process populated by DEGs in Δltp1 involved genome stability. Comparison of the WT strain between the in vitro and in vivo condition indicated that DNA metabolic processes, including recombination and transposition, were significantly upregulated in vivo. Hence, a major role of Ltp1 phosphatase activity at the transcriptional level may be control of adaptation to in vivo conditions. Additionally, both Ltp1 and Php1 have common functions in the control of the expression of genes encoding transporter systems.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"258-264"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883205","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}

{"title":"Streptococcus mutans Collagen-Binding Protein Cnm Is a Multifunctional Adhesin: A Structural Investigation.","authors":"Joshua L Mieher, Norbert Schormann, Ren Wu, Manisha Patel, Sangeetha Purushotham, Jose Lemos, Jacqueline Abranches, Hui Wu, Champion Deivanayagam","doi":"10.1111/omi.70005","DOIUrl":"10.1111/omi.70005","url":null,"abstract":"<p><p>The collagen-binding adhesin Cnm is a known virulence factor of Streptococcus mutans. It is present in specific serotypes (mostly e, f, and k strains) of S. mutans and belongs to the LPXTG family of cell wall-anchored surface adhesins. Here, we report the crystal structure of the collagen-binding N₂ domain of S. mutans Cnm. Using the Staphylococcus aureus collagen-binding protein Cna, which shares high sequence and structural homology with Cnm, we modeled collagen binding to S. mutans Cnm. The comparative analysis identified three conserved collagen-binding residues (Y176, F192, N194) and four equivalent residues that are different in their composition (D224, T226, S232, M276). This study also discovered the multifunctional attributes of this protein, where Cnm-FL, Cnm-N_12, and the individual domains of Cnm-N₁ and Cnm-N₂ adhere with high affinity to the scavenger receptor cysteine-rich (SRCR) domains of glycoprotein 340 (Gp340). Protein-protein docking of Cnm-N₂ and SRCR₁ showed the possibility of a shared binding site at the collagen-binding interface of Cnm-N₂. Furthermore, competition experiments using collagen and SRCR₁₂₃ with Cnm-N₂, Cnm-N_12, and Cnm-FL constructs confirmed that collagen and SRCR₁ share a binding site. Subsequent alanine substitution mutagenesis of the predicted collagen-binding residues validated our modeling results, confirming that Y176 and F192 are important residues for collagen and SRCR/Gp340 binding.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"265-277"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961732","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}

{"title":"Harnessing the Regulatory Effects of Streptococcus mutans Two-Component Signal Transduction Systems for Therapeutic Interventions Against Dental Caries.","authors":"Bingrun Qiu, Yalan Deng, Zhiheng Yi, Yingming Yang, Lei Lei, Tao Hu","doi":"10.1111/omi.70006","DOIUrl":"10.1111/omi.70006","url":null,"abstract":"<p><p>Streptococcus mutans is considered the main pathogen causing dental caries and has a strong ability to establish biofilms and respond to environmental stimuli, which are essential for its survival and cariogenicity. Fourteen two-component signal transduction systems (TCSs) in S. mutans have been reported to regulate a broad range of physiological processes such as bacterial biofilm formation, acid resistance, competence development, and toxic oxygen metabolite resistance. These systems collectively contribute to the cariogenicity of S. mutans by coordinating adaptive responses to environmental challenges. Among them, the VicRK system has been one of the most extensively studied, with epidemiological evidence linking vicK mutations to increased caries risk in children. Other TCSs, such as ComDE, LiaRS, CiaRH, and the orphan response regulator GcrR, also contribute to cariogenicity regulation. The present review summarizes the regulatory roles of TCSs in virulence traits of S. mutans, with an emphasis on those involved in biofilm formation, which highlights their potential as therapeutic targets to prevent dental caries through biofilm inhibition.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"243-257"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961728","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}

{"title":"A Defined Artificial Saliva Medium Allows Characterization of the Hypothiocyanite Response of Streptococcus sanguinis and Streptococcus mutans.","authors":"Avery D Lieber, Drashti Vaghasia, Christopher W Hamm, Michael J Gray","doi":"10.1111/omi.70008","DOIUrl":"10.1111/omi.70008","url":null,"abstract":"<p><p>Hypothiocyanite (OSCN^-/HOSCN) is an antimicrobial molecule found at high concentrations in saliva. HOSCN is thought to differentially affect oral streptococci, since noncariogenic streptococci (e.g. Streptococcus sanguinis) possess HOSCN reductase activity that cariogenic streptococci (e.g. Streptococcus mutans) lack. However, the enzyme responsible for this activity and the effects of HOSCN and HOSCN reductase activity on biofilm formation by oral streptococci have not been previously established. In this work, we developed an artificial saliva medium for growth of oral streptococci with minimal redox-active components, called Defined Recipe Optimized Oral Liquid (DROOL), and used it to characterize the HOSCN responses of S. sanguinis and S. mutans. We identified a homolog of the Streptococcus pneumoniae Har protein in S. sanguinis as HOSCN reductase. S. mutans wild-type and S. sanguinis ∆har mutants were more sensitive to inhibition by physiological concentrations of HOSCN in DROOL than wild-type S. sanguinis when grown planktonically. S. mutans biofilm formation and glucan production were strongly decreased by HOSCN treatment, suggesting HOSCN inhibits S. mutans exopolysaccharide production. Collectively, our data demonstrate the specific ability of HOSCN to inhibit functions of cariogenic but not noncariogenic oral streptococci and show that Har is responsible for mediating this difference.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"289-302"},"PeriodicalIF":3.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12824836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993107","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":"Tolerance Induced by Porphyromonas gingivalis Altered Inflammatory Responses in Mice.","authors":"Miao Yu, Wen-Bo Qian, Yuan-Chun Fang, Yang Chen, Qiao Zhou, Ying Sun","doi":"10.1111/omi.70002","DOIUrl":"10.1111/omi.70002","url":null,"abstract":"<p><p>Tolerance refers to a hyporesponsiveness toward repeated stimulations with bacteria and their virulence factors, which might exist in the development of periodontitis. To identify the roles of tolerance induced by Porphyromonas gingivalis (P. gingivalis) in periodontitis, an original tolerized mice model was established by high-dose of oral P. gingivalis inoculation following a primary infection. The alveolar bone loss of maxillae was detected by Micro-CT. The infiltration of neutrophils and macrophages, and macrophage polarization were detected by IHC and flow cytometry, respectively. Residual P. gingivalis in subgingival plaque with and without macrophage/neutrophil depletion was measured by real-time PCR. Moreover, a real-time PCR chip and bioinformatic analysis were then employed to explore the cytokine expression profiles in gingivae. The abundance of TNF-α, Toll-like receptor 2 (TLR2), and TLR4 were further verified by western blot. In comparison with the non-tolerance group, TNF-α protein levels, alveolar bone loss, and the infiltration of neutrophils and macrophages in the tolerance group were significantly suppressed (p < 0.05), while the quantities of residual P. gingivalis in subgingival plaque were increased (p < 0.05). Moreover, the depletion of macrophages by liposomal clodronate weakened the inhibitory effect of tolerance, as evidenced by the lack of differences in the quantities of residual bacteria between the tolerance and non-tolerance groups (p > 0.05). Macrophages in gingivae of tolerized mice were more likely to polarize into M2 type. In addition, the expressions of cytokines related to neutrophil and macrophage infiltration and recruitment and the protein levels of TLR2 and TLR4 were decreased in tolerized mice (p < 0.05). Tolerance induced by repeated P. gingivalis stimulations suppressed inflammatory responses in periodontal tissues, and the established periodontal tolerance model provided a reliable tool for the further study on periodontal tolerance in vivo.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"223-233"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691009","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}

{"title":"Role of Oral Microbes in Epithelial-Mesenchymal Transition in Cancer Progression.","authors":"Divya Gopinath, Zhengrui Li, Marwan Mansoor Mohammed, Swagatika Panda","doi":"10.1111/omi.70001","DOIUrl":"10.1111/omi.70001","url":null,"abstract":"<p><p>Epithelial-mesenchymal transition (EMT) is a fundamental biological process where epithelial cells lose their polarity and adhesion properties, acquiring mesenchymal characteristics such as enhanced migratory ability and invasiveness. Cells undergoing EMT exhibit enhanced motility, aggressiveness, and stemness, contributing to a pro-tumor environment that facilitates malignant metastasis in cancer. Numerous studies have suggested that oral microbes facilitate carcinogenesis through EMT. Oral microbes can directly initiate EMT by adhering to mucosal layers and provoking the disintegration of intercellular adhesion among epithelial cells, thereby modifying cell polarity and downstream signaling pathways. Indirectly, the microbial metabolites and associated compounds can affect the dynamics of EMT. This review summarizes the mechanisms by which oral microbes regulate EMT and thus contribute significantly to cancer. Elucidating the mechanisms underlying the increased plasticity of cancer cells induced by the oral microbiota will facilitate the development of novel targeted therapeutic strategies.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"191-201"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637582","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}

{"title":"Marine-Derived Cyclo(l-Leucyl-l-Prolyl) Targets d-Alanylation of Lipoteichoic Acid to Combat Streptococcus mutans UA159 Mediated Dental Cariogenesis.","authors":"Ravichellam Sangavi, Nambiraman Malligarjunan, Shunmugiah Karutha Pandian, Shanmugaraj Gowrishankar","doi":"10.1111/omi.70000","DOIUrl":"10.1111/omi.70000","url":null,"abstract":"<p><p>With the growing threat of antimicrobial resistance (AMR), antivirulence strategies present a promising alternative to traditional antibiotics, particularly in dentistry. Dental caries, a chronic biofilm-associated disease primarily driven by the AMR pathogen Streptococcus mutans, results in enamel demineralization and significant oral health challenges. This study explores the anticariogenic mechanism of marine-derived cyclo(l-leucyl-l-prolyl) (CLP), a biomolecule known to inhibit key virulence factors of S. mutans UA159. LC-MS/MS proteomic analysis revealed 30 and 71 significantly regulated proteins following 12 and 24 h of CLP treatment, respectively. Protein-protein interaction and gene ontology analyses demonstrated that CLP downregulates critical virulence proteins related to d-alanylation of lipoteichoic acid (LTA), glucan synthesis, acid production and acid tolerance, while upregulating proteins associated with translation, DNA repair and protein metabolism. KEGG pathway analysis highlighted the involvement of downregulated proteins in key metabolic pathways, including d-alanine metabolism, starch and sucrose metabolism, glycolysis and branched-chain amino acid metabolism. Given the pivotal role of d-alanine metabolism in modulating interconnected virulence pathways, a comparative analysis of in vitro virulence assays-including cell adherence, biofilm formation, acid production and cell surface charge-alongside proteomic data signify that CLP specifically targets the d-alanylation of LTA. This hypothesis was further validated by LTA and d-alanine quantification assays, which confirmed a significant reduction in d-alanine content within LTA after CLP treatment, leading to a marked attenuation of S. mutans cariogenic virulence. Additionally, qPCR and molecular docking analyses corroborated that CLP disrupts S. mutans virulence by interfering with the d-alanylation of LTA. These findings highlight CLP's potential as a novel therapeutic agent for combating dental cariogenesis by targeting S. mutans virulence, offering a promising avenue for the development of advanced anticariogenic therapies.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"202-222"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326312","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}

{"title":"The Secretion and Maturation Journey of Gingipains.","authors":"Zixue Lei, Qizhao Ma, Xuedong Zhou, Yuqing Li","doi":"10.1111/omi.12497","DOIUrl":"10.1111/omi.12497","url":null,"abstract":"<p><p>Multifunctional gingipains are trypsin-like enzymes secreted extracellularly by Porphyromonas gingivalis, which require delicate transit and processing to be activated in different mature forms. This review manages to reconstruct each processing step including the specific cleavage sites and relative proteins or helpers. Errors in any steps can lead to the accumulation of immature gingipains and weaken the virulence of P. gingivalis. Of special note, we emphasize the contribution of new studies to the refinement of the gingipain maturation process and factors that influence their pathogenicity. For example, it is proposed that glutamine cyclase, which is responsible for cyclizing exposed glutamine to pyroglutamic acid after the N-terminal signal peptide is removed, may be able to serve as a potential target for periodontitis treatment, as normal cyclization is key to maintaining the stability of gingipains. Further structural and functional unraveling of the type IX secretion system components, such as the identification of the structure of the PorV-associated shuttle complex, the determination of PorZ's role as the A-LPS deliverer, and the confirmation of the specific mechanism by which PorU promotes CTD removal and catalyzes the transpeptide reaction, has also contributed to a better understanding of gingipain processing. Meanwhile, as the successful activation of gingipains serves to fulfill their functions, this work also concentrates on gingipain pathogenicity, with a particular focus on how gingipains can induce or stimulate the development of systemic diseases, such as causing cardiovascular disorder through vascular damage or exacerbating inflammation in the brain in Alzheimer's disease after crossing the blood-brain barrier.</p>","PeriodicalId":18815,"journal":{"name":"Molecular Oral Microbiology","volume":" ","pages":"177-190"},"PeriodicalIF":3.4,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258591","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}