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Vaccination targeting surface FomA of Fusobacterium nucleatum against bacterial co-aggregation: Implication for treatment of periodontal infection and halitosis.

ABSTRACT: The mechanical therapy with multiple doses of antibiotics is one of modalities for treatment of periodontal diseases. However, treatments using multiple doses of antibiotics carry risks of generating resistant strains and misbalancing the resident body flora. We present an approach via immunization targeting an outer membrane protein FomA of Fusobacterium nucleatum (F. nucleatum), a central bridging organism in the architecture of oral biofilms. Neutralization of FomA considerably abrogated the enhancement of bacterial co-aggregation, biofilms and production of volatile sulfur compounds mediated by an inter-species interaction of F. nucleatum with Porphyromonas gingivalis (P. gingivalis). Vaccination targeting FomA also conferred a protective effect against co-infection-induced gum inflammation. Here, we advance a novel infectious mechanism by which F. nucleatum co-opts P. gingivalis to exacerbate gum infections. FomA is highlighted as a potential target for development of new therapeutics against periodontal infection and halitosis in humans.

SUBMITTER: Liu PF

PROVIDER: S-EPMC2855893 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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Vaccination targeting surface FomA of Fusobacterium nucleatum against bacterial co-aggregation: Implication for treatment of periodontal infection and halitosis.

Liu Pei-Feng PF Shi Wenyuan W Zhu Wenhong W Smith Jeffery W JW Hsieh Shie-Liang SL Gallo Richard L RL Huang Chun-Ming CM

Vaccine 20100226 19

The mechanical therapy with multiple doses of antibiotics is one of modalities for treatment of periodontal diseases. However, treatments using multiple doses of antibiotics carry risks of generating resistant strains and misbalancing the resident body flora. We present an approach via immunization targeting an outer membrane protein FomA of Fusobacterium nucleatum (F. nucleatum), a central bridging organism in the architecture of oral biofilms. Neutralization of FomA considerably abrogated the ...[more]

PMID: 20189489

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Project description:BackgroundInfection with the periodontal pathogen Fusobacterium nucleatum (F. nucleatum) has been associated with gastric cancer. The present study is aimed at uncovering the putative biological mechanisms underlying effects of F. nucleatum-mediated neutrophil transcriptional deregulation in gastric cancer.Materials and methodsA gene expression dataset pertaining to F. nucleatum-infected human neutrophils was utilized to identify differentially expressed genes (DEGs) using the GEO2R tool. Candidate genes associated with gastric cancer were sourced from the "Candidate Cancer Gene Database" (CCGD). Overlapping genes among these were identified as link genes. Functional profiling of the link genes was performed using "g:Profiler" tool to identify enriched Gene Ontology (GO) terms, pathways, miRNAs, transcription factors, and human phenotype ontology terms. Protein-protein interaction (PPI) network was constructed for the link genes using the "STRING" tool, hub nodes were identified as key candidate genes, and functionally enriched terms were determined.ResultsThe gene expression dataset GEO20151 was downloaded, and 589 DEGs were identified through differential analysis. 886 candidate gastric cancer genes were identified in the CGGD database. Among these, 36 overlapping genes were identified as the link genes. Enriched GO terms included molecular function "enzyme building," biological process "protein folding,'" cellular components related to membrane-bound organelles, transcription factors ER71 and Sp1, miRNAs miR580 and miR155, and several human phenotype ontology terms including squamous epithelium of esophagus. The PPI network contained 36 nodes and 53 edges, where the top nodes included PH4 and CANX, and functional terms related to intracellular membrane trafficking were enriched.ConclusionF nucleatum-induced neutrophil transcriptional activation may be implicated in gastric cancer via several candidate genes including DNAJB1, EHD1, IER2, CANX, and PH4B. Functional analysis revealed membrane-bound organelle dysfunction, intracellular trafficking, transcription factors ER71 and Sp1, and miRNAs miR580 and miR155 as other candidate mechanisms, which should be investigated in experimental studies.

Dataset Information

Vaccination targeting surface FomA of Fusobacterium nucleatum against bacterial co-aggregation: Implication for treatment of periodontal infection and halitosis.

Publications

Vaccination targeting surface FomA of Fusobacterium nucleatum against bacterial co-aggregation: Implication for treatment of periodontal infection and halitosis.

Similar Datasets

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