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Vaccination targeting surface FomA of Fusobacterium nucleatum against bacterial co-aggregation: Implication for treatment of periodontal infection and halitosis |
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| Authors: | Pei-Feng Liu Wenyuan Shi Wenhong Zhu Jeffery W Smith Shie-Liang Hsieh Richard L Gallo Chun-Ming Huang |
| Institution: | 1. Department of Medicine, Division of Dermatology, University of California, San Diego, CA 92161, USA;2. VA San Diego Healthcare Center, San Diego, CA 92161, USA;3. School of Dentistry and Molecular Biology Institute and Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA;4. Burnham Institute for Medical Research, La Jolla, CA 92037, USA;5. Department and Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan;6. Moores Cancer Center, University of California, San Diego, CA 92093, USA |
| 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. |
| Keywords: | ATCC American Type Culture Collection CFU colony forming unit DLS dynamic light scattering DTS dispersion technology software E coli Escherichia coli ELISA enzyme-linked immunosorbent assay EM electron microscopy FITC fluorescein isothiocyanate F nucleatum Fusobacterium nucleatum FomA outer membrane protein of Fusobacterium nucleatum GFP green fluorescent protein H& E hematoxylin & eosin HRP horseradish peroxidase H2S hydrogen sulfide ICR Institute of Cancer Research IgG immunoglobulin G IL interleukin IPTG isopropyl-β-d-thiogalactoside LB Luria-Bertani MIP-2 macrophage-inflammatory protein-2 NIH National Institutes of Health OE oral epithelium OHO-C oral hydrogen sulfide-producing organism plate PBS phosphate-buffered saline PCR polymerase chain reaction PVDF polyvinylidene fluoride P gingivalis Porphyromonas gingivalis SDS sodium dodecyl sulfate SDS-PAGE SDS-polyacrylamide gel electrophoresis S-IgA secretory immunoglobulin A S mutans Streptococcus mutans Th1 T-helper type 1 Th2 T-helper type 2 TSB trypticase soy broth VSCs volatile sulfur compounds UV ultraviolet |
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