VimA mediates multiple functions that control virulence in Porphyromonas gingivalis

Abstract

Porphyromonas gingivalis, a black-pigmented, gram-negative anaerobe, is an important etiological agent of periodontal disease. Its ability to survive in the periodontal pocket and orchestrate the microbial/host activities that can lead to disease suggest that P. gingivalis possesses a complex regulatory network involving transcriptional and post-transcriptional mechanisms. The vimA (virulence modulating) gene is part of the 6.15-kb bcp-recA-vimA-vimE-vimF-aroG locus and plays a role in oxidative stress resistance. In addition to the glycosylation and anchorage of several surface proteins including the gingipains, VimA can also modulate sialylation, acetyl coenzyme A transfer, lipid A and its associated proteins and may be involved in protein sorting and transport. In this review, we examine the multifunctional role of VimA and discuss its possible involvement in a major regulatory network important for survival and virulence regulation in P. gingivalis. It is postulated that the multifunction of VimA is modulated via a post-translational mechanism involving acetylation.

Figure 1. Genome architecture of bcp- aroG locus in P. gingivalis

Genome architecture of bcp- aroG locus in Porphyromonas gingivalis showing the annotation of the genes (top panel) and their putative functions (bottom panel).

Figure 2. Functions of VimA in surface biogenesis

Multifunction of VimA in various cell surface modifications. Right panel shows the VimA functions and the left panel shows various surface structures.

Figure 3. Common C- terminal domain architecture of VimA interacting proteins and reported CTD proteins

Common C- terminal domain (CTD) architecture of VimA interacting proteins and CTD proteins showing three consensus conserved LxxG, YDMNGRx, G-G-Cterm motifs.

Figure 4. Domain architecture of VimA

Domain architecture of VimA showing conserved acetyl transferase domain, N-acetyl transferase superfamily domain between positions 138 and 257, and a PEP-Cterm domain between amino acid positions 60 and 138.

Figure 5. Operon function of vimA showing modulation of other related genes

vimA regulates fimA and fimbrial expression (Osbourne et al., 2010). amino acid tRNA synthase, alanine tRNA synthase and isoleucine tRNA synthase are involved in transport of amino acids and formation of interpeptide bridges of peptidoglycans (Osbourne et al., 2010; Aruni et al., 2011a). vimA interacts with vimF in glycosylation of surface sugars and peptidoglycan synthesis. In association with vimA, vimE and vimF are involved in gingipain maturation and secretion (Vanterpool et al., 2005a, 2005b). vimA modulates glycan modification and sialidase activity (Aruni et al., 2011b). vimA is involved in acetylation of proteins, lipid biogenesis and mediates protein sorting (Aruni et al., 2011a; Osbourne et al., 2012). vimA is involved in autoaggregation and hemagglutination and thereby in virulence modulation (Vanterpool et al., 2004, 2006; Osbourne et al., 2010).