The oral cavity harbors a complex microbial biofilm community capable of mediating acute and chronic polymicrobial infections including periodontal diseases which are still the most common reason for tooth loss worldwide. Specific interspecies interactions are key factors in constructing these communities and Fusobacterium nucleatum (Fn) has been established as the central "bridging" organism that enables arrangement of numerous oral bacterial species (both "early" and "late" colonizers) into well organized communities for biofilm formation and pathogenesis. The ability of Fn to adhere to a large variety of oral species has been clearly demonstrated through elaborate in vitro co-aggregation studies with planktonic cells, yet only limited studies have explored how this ability manifests in multispecies microbial biofilms. More importantly, lack of effective genetic manipulation tools and clear molecular targets has hampered investigation of the molecular mechanisms behind these Fn-mediated fascinating interspecies interactions. We recently achieved the first genetic characterization of a fusobacterial adhesin (RadD) that mediates interspecies adhesion with early oral colonizers. In our preliminary studies, we demonstarted that RadD- dependent binding to its partner species Streptococcus sanguinis (Ss) stimulates distinct phenotypic changes and differential gene expression in Fn. Based on these findings, we developed our working hypothesis that "Fn interacts via RadD and associated Rad-proteins with early colonizing partner species, which triggers significant morphological and physiological changes in Fn important for biofilm formation". To test this hypothesis, we propose a detailed examination of the role of RadD in Fn-mediated interspecies interactions using Streptococcus sanguinis (Ss) as model early colonizing partner species. Approaches will include characterization of biofilm behavior, oral community integration, gene expression patterns and identification of cellular components in Ss involved in the OMP-mediated interaction with Fn. This comprehensive approach will provide detailed knowledge at the molecular level for the events involved in biofilm formation including physical cell-cell contact and signaling. This research will provide novel targets for improved therapeutic intervention of a widespread human infectious disease and serve as a basis for future studies of Fn with late colonizing partner species or animal models.
Fusobacterium nucleatum (Fn) is a bacterium with key functions in building oral biofilms in the gingival pocket through its ability to stick to a large variety of other bacteria. These bacteria include the ones that grow on oral tissue and tooth surfaces as well as important periodontal pathogens. The detailed understanding of how Fn binds to the surface attached bacteria will provide an important basis for improved therapeutics against periodontitis since it enables the recruitment of pathogenic bacteria into the oral bacterial plaque community.
|Bhattacharyya, Sanghamitra; Ghosh, Santosh K; Shokeen, Bhumika et al. (2016) FAD-I, a Fusobacterium nucleatum Cell Wall-Associated Diacylated Lipoprotein That Mediates Human Beta Defensin 2 Induction through Toll-Like Receptor-1/2 (TLR-1/2) and TLR-2/6. Infect Immun 84:1446-56|
|Wu, T; Cen, L; Kaplan, C et al. (2015) Cellular Components Mediating Coadherence of Candida albicans and Fusobacterium nucleatum. J Dent Res 94:1432-8|
|He, Xuesong; McLean, Jeffrey S; Edlund, Anna et al. (2015) Cultivation of a human-associated TM7 phylotype reveals a reduced genome and epibiotic parasitic lifestyle. Proc Natl Acad Sci U S A 112:244-9|
|Kaplan, Aida; Kaplan, Christopher W; He, Xuesong et al. (2014) Characterization of aid1, a novel gene involved in Fusobacterium nucleatum interspecies interactions. Microb Ecol 68:379-87|
|Sarkar, Juni; McHardy, Ian H; Simanian, Emil J et al. (2014) Transcriptional responses of Treponema denticola to other oral bacterial species. PLoS One 9:e88361|
|He, Xuesong; McLean, Jeffrey S; Guo, Lihong et al. (2014) The social structure of microbial community involved in colonization resistance. ISME J 8:564-74|
|Edlund, Anna; Yang, Youngik; Hall, Adam P et al. (2013) An in vitro biofilm model system maintaining a highly reproducible species and metabolic diversity approaching that of the human oral microbiome. Microbiome 1:25|
|Wu, Tingxi; Hu, Wei; Guo, Lihong et al. (2013) Development of a new model system to study microbial colonization on dentures. J Prosthodont 22:344-50|
|He, Xuesong; Hu, Wei; Kaplan, Christopher W et al. (2012) Adherence to streptococci facilitates Fusobacterium nucleatum integration into an oral microbial community. Microb Ecol 63:532-42|
|Wang, Ren-ke; He, Xue-song; Hu, Wei et al. (2011) Analysis of interspecies adherence of oral bacteria using a membrane binding assay coupled with polymerase chain reaction-denaturing gradient gel electrophoresis profiling. Int J Oral Sci 3:90-7|
Showing the most recent 10 out of 11 publications