, a black-pigmented, Gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease (22), rheumatoid arthritis (6,19) and other systemic diseases. The recent designation of P. gingivalis as a "keystone pathogen" (31) further highlights its ability to adapt to the harsh inflammatory conditions of the periodontal pocket and disrupt host-microbial homeostasis, which is partly responsible for the pathology observed in periodontal disease. Thus, to survive and orchestrate the microbial/host activities that can lead to disease, suggest that P. gingivalis possesses a complex regulatory network probably involving transcriptional and post-transcriptional mechanisms. While a key element in modulating the pathogenic potential of P. gingivalis is the post- translational modification of several of the major surface proteins/structures, there is a gap in our understanding of the components and mechanism(s) of this circuitry. The specific hypothesis to be addressed in this application is that via acetylation the novel vimA (virulence modulating) gene product is involved in the post-translational control of several major surface proteins in P. gingivalis including gingipain maturation/activation. In addition, VimA can also modulate the expression of several virulence genes by a transcriptional mechanism. This hypothesis is based on the observations made in the previous funding period where we have characterized the bcp-recA-vimA-vimE-vimF-aroG locus. This operon is essential for the maturation/activation/anchorage of the gingipains and regulation of other virulence factors of P. gingivalis. VimA is also important in oxidative stress resistance (4). Our data support a multifunctional role for VimA in modulating virulence in P. gingivalis possibly through its involvement in acetylation, that may affect A-LPS synthesis, protein sorting/transfer/anchorage and gene expression. In this project, we wish to extend these findings and to more fully clarify the VimA-dependent mechanism(s) of virulence regulation via acetylation. In bacteria including oral pathogens, the role of acetylation in virulence regulation has not been well characterized. The long term objective of our research program is to elucidate a comprehensive molecular mechanism(s) for virulence regulation in P. gingivalis as a prerequisite to the development of novel therapeutic interventions to aid in the control and prevention of diseases associated with this keystone pathogen. It is likely that VimA, which is involved in acetylation, may be a founding member of a novel transcriptional/post-translational control mechanism in Gram- negative anaerobic bacteria. The current application is designed for a comprehensive assessment of the multifunctional role of VimA.
The specific aims : (1) To evaluate the role of acetylation in protein maturation in P. gingivalis. (2) To explore the effectsof VimA-dependent acetylation on gene expression in P. gingivalis. Collectively, the results from this study will clarify the mechanistic role of VimA in virulence regulation in P. gingivalis. It should shed light on the acetylation regulatory network in P. gingivalis. It will generate a model system(s) that will yield important clues that will facilitate the development of novel therapeutic interventions to aid in the control and prevention of periodontal disease.
The post-translational modification of several of the major surface proteins/structures is important for the pathogenic potential of P. gingivalis. The goal of this research is to characterize the novel VimA-dependent mechanism for virulence regulation in P. gingivalis via acetylation. Because of the success of this bacterium as an important cause of gum disease suggests that these systems are vital for its survival. Essential components of this regulatory system are prime targets for the development of novel therapeutics that will have a positive impact on human health.
|Dou, Y; Aruni, W; Muthiah, A et al. (2016) Studies of the extracytoplasmic function sigma factor PG0162 in Porphyromonas gingivalis. Mol Oral Microbiol 31:270-83|
|Boutrin, M-C; Yu, Y; Wang, C et al. (2016) A putative TetR regulator is involved in nitric oxide stress resistance in Porphyromonas gingivalis. Mol Oral Microbiol 31:340-53|
|McKenzie, Rachelle M E; Henry, Leroy G; Boutrin, Marie-Claire et al. (2016) Role of the Porphyromonas gingivalis iron-binding protein PG1777 in oxidative stress resistance. Microbiology 162:256-67|
|Chioma, O; Aruni, A W; Milford, T-A et al. (2016) Filifactor alocis collagenase can modulate apoptosis of normal oral keratinocytes. Mol Oral Microbiol :|
|Aruni, A Wilson; Mishra, Arunima; Dou, Yuetan et al. (2015) Filifactor alocis--a new emerging periodontal pathogen. Microbes Infect 17:517-30|
|Dou, Y; Robles, A; Roy, F et al. (2015) The roles of RgpB and Kgp in late onset gingipain activity in the vimA-defective mutant of Porphyromonas gingivalis W83. Mol Oral Microbiol 30:347-60|
|McKenzie, R M E; Aruni, W; Johnson, N A et al. (2015) Metabolome variations in the Porphyromonas gingivalis vimA mutant during hydrogen peroxide-induced oxidative stress. Mol Oral Microbiol 30:111-27|
|Dou, Yuetan; Aruni, Wilson; Luo, Tianlong et al. (2014) Involvement of PG2212 zinc finger protein in the regulation of oxidative stress resistance in Porphyromonas gingivalis W83. J Bacteriol 196:4057-70|
|Aruni, A Wilson; Zhang, Kangling; Dou, Yuetan et al. (2014) Proteome analysis of coinfection of epithelial cells with Filifactor alocis and Porphyromonas gingivalis shows modulation of pathogen and host regulatory pathways. Infect Immun 82:3261-74|
|Seiberling, Kristin A; Aruni, Wilson; Kim, Shawn et al. (2013) The effect of intraoperative mupirocin irrigation on Staphylococcus aureus within the maxillary sinus. Int Forum Allergy Rhinol 3:94-8|
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