regT can modulate gingipain activity and response to oxidative stress in Porphyromonas gingivalis

Vanterpool, Elaine; Aruni, Wilson; Roy, Francis; Fletcher, Hansel M.

doi:10.1099/mic.0.038315-0

Cited by 9 publications

(12 citation statements)

References 45 publications

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“…These include antioxidant enzymes [45], Dps [69], the hemin layer [7] and enzymatic removal of deleterious products (e.g., 8-oxoguanine) caused by ROS [4,6,38]. Additionally, several response regulators have been implicated in oxidative stress resistance [17,18,86]. Taken together, there is no doubt that P. gingivalis is a robust organism that has developed numerous strategies to survive in the harsh environment of the periodontal pocket.…”

Section: Resultsmentioning

confidence: 99%

“…These studies showed that ECF-σ factors could likely modulate the virulence potential of P. gingivalis , leading to oxidative stress resistance. There is also emerging evidence of a unique regulatory mechanism(s) for gingipain biogenesis in P. gingivalis (PG2096, designated regT ) that plays a role in regulating the gingipains at elevated temperatures [18]. RegT was shown to be involved in resistance to oxidative stress in P. gingivalis ; however, the exact mechanism is still unclear.…”

Section: Regulators Of Oxidative Stressmentioning

confidence: 99%

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Oxidative Stress Resistance in Porphyromonas Gingivalis

et al. 2012

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Porphyromonas gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiologic agent of periodontal disease. The harsh inflammatory condition of the periodontal pocket implies that this organism has properties that will facilitate its ability to respond and adapt to oxidative stress. Because the stress response in the pathogen is a major determinant of its virulence, a comprehensive understanding of its oxidative stress resistance strategy is vital. We discuss multiple mechanisms and systems that clearly work in synergy to defend and protect P. gingivalis against oxidative damage caused by reactive oxygen species. The involvement of multiple hypothetical proteins and/or proteins of unknown function in this process may imply other unique mechanisms and potential therapeutic targets.

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Section: Resultsmentioning

confidence: 99%

Section: Regulators Of Oxidative Stressmentioning

confidence: 99%

Oxidative Stress Resistance in Porphyromonas Gingivalis

et al. 2012

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“…Several genes, including porR, gftB, rfa, ugdA, vimE, and vimF, have shown the importance of the O side chain polysaccharide (O-LPS) and anionic polysaccharide (A-LPS) in these processes (50,53,(61)(62)(63)66). A defect in some of these genes resulted in a complete loss of surface-associated gingipain proteinases, strong autoaggregation, and a marked increase in biofilm formation.…”

Section: Discussionmentioning

confidence: 99%

“…Because the specific functional roles of the vim genes are not yet fully defined, we cannot rule out the possibility that their modulation of other proteins could have similar mechanistic properties. Protein-protein interaction studies using the purified recombinant VimA (rVimA) showed that this protein can interact with the gingipains, HtrA, RegT, sialidase, and other proteins in P. gingivalis (2,47,61,64). Also, in addition to its role in glycosylation, the VimA protein can affect capsular synthesis, fimbrial phenotypic expression, and anchorage of several cell surface proteins (44).…”

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confidence: 99%

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

et al. 2012

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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. Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is one of the main etiological agents of adult periodontitis. While several virulence factors, including fimbriae (28), hemagglutinin (17), capsule (4), and lipopolysaccharide (68), have been implicated in the pathogenicity of P. gingivalis, the strong proteolytic abilities of this organism are considered to be important for its survival and thus play a significant role in virulence (12, 63). The major proteases, called gingipains, consist of arginine-specific (Arg-gingipain [Rgp]) and lysine-specific (Lysgingipain [Kgp]) proteases that are both extracellular and cell membrane associated (32). The activation of these gingipains is associated with several genes, including vimA, vimE, and vimF, that modulate the posttranslational glycosylation of those proteins (44,(62)(63)(64). These genes are part of the 6. locus which has previously been shown to be important to the pathogenic potential of P. gingivalis (1,26,44,(62)(63)(64).We have demonstrated that the bcp and recA genes play the expected role in oxidative stress resistance and DNA repair, respectively (26). The association of these genes with the vim genes on the same transcriptional unit could be considered an important strategy for P. gingivalis to coordinate its oxidative stress and proteolytic activities. A response to oxidative stress will involve binding of oxygen and its toxic derivativ...

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“…Further, the posttranslational addition of carbohydrates to the gingipains is highly variable, thus implying a role for multiple factors in this process (10). We previously reported that the VimA protein, which can modulate gingipain activity in P. gingivalis, can also interact with a putative sialidase protein (1,30,50,53). Although sialylation can be involved in protein maturation, its role, if any, in gingipain maturation/activation is unknown.…”

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confidence: 99%

Sialidase and Sialoglycoproteases Can Modulate Virulence in Porphyromonas gingivalis

et al. 2011

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The Porphyromonas gingivalis recombinant VimA can interact with the gingipains and several other proteins, including a sialidase. Sialylation can be involved in protein maturation; however, its role in virulence regulation in P. gingivalis is unknown. The three sialidase-related proteins in P. gingivalis showed the characteristic sialidase Asp signature motif (SXDXGXTW) and other unique domains. To evaluate the roles of the associated genes, randomly chosen P. gingivalis isogenic mutants created by allelic exchange and designated FLL401 (PG0778::ermF), FLL402 (PG1724::ermF), and FLL403 (PG0352::ermF-ermAM) were characterized. Similar to the wild-type strain, FLL402 and FLL403 displayed a black-pigmented phenotype in contrast to FLL401, which was not black pigmented. Sialidase activity in P. gingivalis FLL401 was reduced by approximately 70% in comparison to those in FLL402 and FLL403, which were reduced by approximately 42% and 5%, respectively. Although there were no changes in the expression of the gingipain genes, their activities were reduced by 60 to 90% in all the isogenic mutants compared to that for the wild type. Immunoreactive bands representing the catalytic domains for RgpA, RgpB, and Kgp were present in FLL402 and FLL403 but were missing in FLL401. While adhesion was decreased, the capacity for invasion of epithelial cells by the isogenic mutants was increased by 11 to 16% over that of the wild-type strain. Isogenic mutants defective in PG0778 and PG0352 were more sensitive to hydrogen peroxide than the wild type. Taken together, these results suggest that the P. gingivalis sialidase activity may be involved in regulating gingipain activity and other virulence factors and may be important in the pathogenesis of this organism.

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regT can modulate gingipain activity and response to oxidative stress in Porphyromonas gingivalis

Cited by 9 publications

References 45 publications

Oxidative Stress Resistance in Porphyromonas Gingivalis

Oxidative Stress Resistance in Porphyromonas Gingivalis

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

Sialidase and Sialoglycoproteases Can Modulate Virulence in Porphyromonas gingivalis

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