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

Abstract

ABSTRACTThePorphyromonas gingivalisVimA protein has multifunctional properties that can modulate several of its major virulence factors. To further characterize VimA,P. gingivalisFLL406 carrying an additionalvimAgene and avimA-defective mutant in a differentP. gingivalisgenetic background were evaluated. ThevimA-defective mutant (FLL451) in theP. gingivalisATCC 33277 genetic background showed a phenotype similar to that of thevimA-defective mutant (FLL92) in theP. gingivalisW83 genetic background. In contrast to the wild type, gingipain activity was increased inP. gingivalisFLL406, avimAchimeric strain.P. gingivalisFLL451 had a five times higher biofilm-forming capacity than the parent strain. HeLa cells incubated withP. gingivalisFLL92 showed a decrease in invasion, in contrast toP. gingivalisFLL451 and FLL406, which showed increases of 30 and 40%, respectively. VimA mediated coenzyme A (CoA) transfer to isoleucine and reduced branched-chain amino acid metabolism. The lipid A content and associated proteins were altered in thevimA-defective mutants. The VimA chimera interacted with several proteins which were found to have an LXXTG motif, similar to the sorting motif of Gram-positive organisms. All the proteins had an N-terminal signal sequence with a putative sorting signal of L(P/T/S)X(T/N/D)G and two unique signatures of EXGXTX and HISXXGXG, in addition to a polar tail. Taken together, these observations further confirm the multifunctional role of VimA in modulating virulence possibly through its involvement in acetyl-CoA transfer and lipid A synthesis and possibly by protein sorting.