VimA-Dependent Modulation of Acetyl Coenzyme A Levels and Lipid A Biosynthesis Can Alter Virulence in Porphyromonas gingivalis

ThePorphyromonas gingivalisVimAprotein hasmultifunctional properties that canmodulate several of itsmajor virulence factors. To further characterize VimA,P. gingivalis FLL406 carrying an additional vimA gene and a vimA-defectivemutant in a differentP. gingivalis genetic backgroundwere evaluated. The vimA-defectivemutant (FLL451) in theP. gingivalisATCC33277 genetic back-ground showed a phenotype similar to that of the vimA-defectivemutant (FLL92) in theP. gingivalisW83 genetic background. In con-trast to thewild type, gingipain activity was increased inP. gingivalis FLL406, a vimA chimeric strain.P. gingivalis FLL451 had a five times higher biofilm-forming capacity than the parent strain.HeLa cells incubatedwithP. gingivalis FLL92 showed a decrease in inva-sion, in contrast toP. gingivalis FLL451 and FLL406, which showed increases of 30 and 40%, respectively. VimAmediated coenzymeA (CoA) transfer to isoleucine and reduced branched-chain amino acidmetabolism. The lipidA content and associated proteinswere altered in the vimA-defectivemutants. TheVimA chimera interactedwith several proteinswhichwere found to have an LXXTGmotif, similar to the sortingmotif ofGram-positive organisms. All the proteins had anN-terminal signal sequencewith a putative sorting signal ofL(P/T/S)X(T/N/D)G and two unique signatures of EXGXTX andHISXXGXG, in addition to a polar tail. Taken to-gether, these observations further confirm the multifunctional role of VimA inmodulating virulence possibly through its in-volvement in acetyl-CoA transfer and lipid A synthesis and possibly by protein sorting. Porphyromonas gingivalis, a Gram-negative anaerobic bacte-rium, is one of the main etiological agents of adult periodon-titis. While several virulence factors, including fimbriae (28)