The processing or Atractylenolide-III expression of various virulence factors including major fimbriae, biofilm production, and the maturation and proper localization of gingipains. Therefore, we hypothesized that PG0717 may modulate the virulence of W83 through a similar mechanism, namely, regulation of virulence factor expression or processing. Of the proteases that P. gingivalis produces, the most noteworthy are a set of cysteine 
proteases referred to as gingipains. These molecules occur as both cell-associated and secreted forms. One type of gingipain cleaves at lysine residues, whereas two other proteases cleave proteins at Gomisin-D arginine residues. The gingipains share extensive amino acid sequence homology with each other and with the major hemagglutinin HagA. These molecules, and a number of others, share a C-terminal domain that is thought to be critical to their transport through the outer membrane via a unique transport system and attachment to the outer membrane. In addition to gingipains, other surface entities are known to affect the virulence of P. gingivalis. The lipid A moiety of the bacterial lipopolysaccharide of P. gingivalis has been reported to influence the innate immune response, and thereby cytokine production, by its effect on Toll-like receptors. Alterations in the structure of lipid A, including number of attached acyl and phosphate groups, can change the bacterial interaction with host cells from merely immune-evasive to actively immune-suppressing. The capsular polysaccharide, which is not found on all strains of P. gingivalis has been demonstrated to both alter cytokine production in cultured host cells and influence the ability of the bacteria to disseminate in vivo The role of PG0717 as a potential virulence factor has not been determined. However, previous observations in our laboratory suggest that PG0717 may be involved in early host/ pathogen interactions. Specifically, we have observed that expression of PG0717 in W83 is significantly up-regulated during the first hour of invasion in human coronary artery endothelial cells. Therefore, in order to determine the pathogenic potential of PG0717, we constructed an isogenic mutant in W83 and assessed its effects on HCAEC. Deletion of PG0717 produced a pleiotropic mutant with an altered virulence phenotype. Further, infection of HCAEC elicited a more pronounced inflammatory response in these cells than its wild type counterpart. HCAEC responses to W83��717 could not be attributed to the capsule or lipid A structure of this mutant since it did not exhibit any alterations in these structures. However, W83��717 displayed a significant reduction in both Kgp and total Rgp gingipains activity. This coincided with decreased RgpA and RgpB protein levels in the proteome profile of W83��717. Quantitative proteome profiling of W83��717 also revealed decreased protein levels of other putative virulence factors including peptidylarginine deiminase and Clp protease. Important features of P. gingivalis mediated disease include the ability of the microbe to attach and invade host cells, disseminate through host tissues, and subvert host immunological surveillance and defense mechanisms. These features are largely executed through well characterized virulence factors such as cysteine proteases, fimbriae, lipopolysaccharide, capsule, and hemagglutinins that exert their effects through direct interactions with the host. In addition, P. gingivalis can modulate its pathogenicity by regulating the expression or processing of its virulence properties. Examples of this mode of regulation include VimA and the GppX two-component sensor kinase system, which regulate the production or processing of gingipains and/or fimbriae.