title: VimA-dependent modulation of acetyl coenzyme A levels and lipid A biosynthesis can alter virulence in Porphyromonas gingivalis.
abstract: The Porphyromonas gingivalis VimA protein has multifunctional properties that can modulate several of its major virulence factors. To further characterize VimA, P. gingivalis FLL406 carrying an additional vimA gene and a vimA-defective mutant in a different P. gingivalis genetic background were evaluated. The vimA-defective mutant (FLL451) in the P. gingivalis ATCC 33277 genetic background showed a phenotype similar to that of the vimA-defective mutant (FLL92) in the P. gingivalis W83 genetic background. In contrast to the wild type, gingipain activity was increased in P. gingivalis FLL406, a vimA chimeric strain. P. gingivalis FLL451 had a five times higher biofilm-forming capacity than the parent strain. HeLa cells incubated with P. gingivalis FLL92 showed a decrease in invasion, in contrast to P. gingivalis FLL451 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 the vimA-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.
authors.affiliation: Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, California, USA.
authors.forename: A Wilson
authors.initials: AW
authors.lastname: Aruni
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: D
authors.initials: D
authors.lastname: Osbourne
authors.forename: Y
authors.initials: Y
authors.lastname: Dou
authors.forename: F
authors.initials: F
authors.lastname: Roy
authors.forename: A
authors.initials: A
authors.lastname: Muthiah
authors.forename: D S
authors.initials: DS
authors.lastname: Boskovic
authors.forename: H M
authors.initials: HM
authors.lastname: Fletcher
mesh_terms: D000105:Acetyl Coenzyme A / Q000235:genetics / Q000378:metabolism*; D018829:Adhesins, Bacterial / Q000378:metabolism; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003599:Cytoskeleton; D004847:Epithelial Cells / Q000166:cytology / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D000080867:Gingipain Cysteine Endopeptidases; D006367:HeLa Cells; D006801:Humans; D007532:Isoleucine / Q000378:metabolism; D008050:Lipid A / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009439:Neuraminidase / Q000378:metabolism; D010802:Phylogeny; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D021381:Protein Transport; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D000596:Amino Acids; D001426:Bacterial Proteins; D000080867:Gingipain Cysteine Endopeptidases; D008050:Lipid A; D007532:Isoleucine; D000105:Acetyl Coenzyme A; D009439:Neuraminidase; D003546:Cysteine Endopeptidases