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There also are oral virulence factors that have multiple functions, such as both the adhesion and serum resistance functions in YadA (84), which has been identified in the oral virome. Phage carrying yadA have been shown to persist in the oral cavity over [http://www.selleckchem.com/products/isrib-trans-isomer.html Selleck ISRIB] relatively long time periods (22). Many different virulence genes such as pblA, pblB, pspA, and yadA have been identified in oral phage using metagenomics; however, the actual contribution of these genes to the pathogenicity of their hosts has yet to be demonstrated experimentally. Phage attachment and traversal of mucosal surfaces The total surface area of the average human mouth is estimated to be 215��13 cm2, with 30.5% of the surface area devoted to the teeth and hard palate, and 69.5% devoted to the tongue and other mucosa (85). This surface area may be increased in periodontal pockets in subjects with severe generalized periodontal disease [http://en.wikipedia.org/wiki/Coagulation Tasisulam] (86). The oral mucosa provides a broad surface area to house phage communities, but membership of mucosal phage communities have yet to be investigated. Because saliva and dental plaque share a portion of their phage (23, 31), it is likely that some phage inhabiting mucosal surfaces also are shared with saliva. The phage to bacteria ratio in the human gums is estimated to be >35:1 compared to a [http://www.selleckchem.com/screening/inhibitor-library.html Inhibitor Library] of virions. The potential for phage virions to be highly persistent in mucus layers could have consequences for their hosts, and phage have been hypothesized to provide a protective function for the human host against invading bacterial pathogens (Fig. 2, Panel a) (87, 88). Fig. 2 Diagrams representing modalities by which phage may alter the diversity of the bacterial community in the human oral cavity. Panel a represents the abundance of phage capable of binding to the oral mucosa. In this example, the phage employ generalist ... Phage nucleic acids have been identified in the blood of individuals who are immunosuppressed (89), which suggests mucosal barriers, and their associated immune components play a role in limiting the access of phage to the bloodstream. While many of the phage identified in the blood may gain access to the blood by way of the gastrointestinal tract, the large surface area of the oral cavity (85) suggests that breaches in the oral mucosa could also lead to translocation of phage into the bloodstream.