Glycosylation of the Arg-gingipains of Porphyromonas gingivalis and Comparison with Glycoconjugate Structure and Synthesis in other Bacteria

Gallagher, Alexandra; Aduse‐Opoku, Joseph; Rangarajan, Minnie; Slaney, J. M.; Curtis, Michael A.

doi:10.2174/1389203033486974

Cited by 34 publications

(43 citation statements)

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“…Glycosylation is a post-translational regulatory mechanism that is important in gingipain biogenesis in P. gingivalis (Gallagher et al, 2003;Curtis et al, 1999;Vanterpool et al, 2005a, b). Further, the post-translational addition of carbohydrates to the gingipains is highly variable, thus implicating a role for multiple factors in this process.…”

Section: Discussionmentioning

confidence: 99%

“…This regulation can occur at multiple levels, including expression of the protease genes, secretion, processing of an inactive secreted precursor to its active form and/or the posttranslational glycosylation of the proteins (Gallagher et al, 2003;Bosques et al, 2004). The multiple layers of regulation are vital to ensure that expression is tightly controlled in the appropriate temporal and spatial patterns.…”

Section: Introductionmentioning

confidence: 99%

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VimA is part of the maturation pathway for the major gingipains of Porphyromonas gingivalis W83

et al. 2006

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The authors have shown previously that the vimA gene, which is part of the bcp-recA-vimA operon, plays an important role in protease activation in Porphyromonas gingivalis. The gingipain RgpB proenzyme is secreted in the vimA-defective mutant P. gingivalis FLL92. An important question that is raised is whether the vimA gene product could directly interact with the proteases for their activation or regulate a pathway responsible for protease activation. To further study the mechanism(s) of VimA-dependent protease activation, the vimA gene product was further characterized. A 39 kDa protein consistent with the size of the predicted VimA protein was purified. In protein–protein interaction studies, the VimA protein was shown to interact with gingipains RgpA, RgpB and Kgp. Immune sera from mice immunized with P. gingivalis immunoreacted with the purified VimA protein. Taken together, these data suggest an interaction of VimA with the gingipains and further confirm the role of this protein in their regulation or maturation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

VimA is part of the maturation pathway for the major gingipains of Porphyromonas gingivalis W83

et al. 2006

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“…S1). PorS is encoded in the porR locus and presents homology to members of the Wzx flippase family (27,28). First, we tested the flippase activity of porS.…”

Section: Mutation In Pors Flippase Affects A-lps Biosynthesis-thementioning

confidence: 99%

Selective Sorting of Cargo Proteins into Bacterial Membrane Vesicles

Haurat¹,

Aduse‐Opoku

Rangarajan

et al. 2011

Journal of Biological Chemistry

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269

290

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In contrast to the well established multiple cellular roles of membrane vesicles in eukaryotic cell biology, outer membrane vesicles (OMV) produced via blebbing of prokaryotic membranes have frequently been regarded as cell debris or microscopy artifacts. Increasingly, however, bacterial membrane vesicles are thought to play a role in microbial virulence, although it remains to be determined whether OMV result from a directed process or from passive disintegration of the outer membrane. Here we establish that the human oral pathogen Porphyromonas gingivalis has a mechanism to selectively sort proteins into OMV, resulting in the preferential packaging of virulence factors into OMV and the exclusion of abundant outer membrane proteins from the protein cargo. Furthermore, we show a critical role for lipopolysaccharide in directing this sorting mechanism. The existence of a process to package specific virulence factors into OMV may significantly alter our current understanding of host-pathogen interactions.

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“…There is emerging evidence that this process may also be important in gingipain biogenesis in P. gingivalis (60,213,214,215). For glycosylation, different glycosyl transferases catalyze the transfer of different carbohydrate moieties from active donors to specific acceptors (including lipids, proteins and nucleic acids) (26).…”

Section: Gingipain Glycosylationmentioning

confidence: 99%

“…Most of the LPS-like glycan moieties appear to occur at the C-terminus of the polypeptide chain and seem to serve to anchor the gingipain molecule into the outer membrane (146,178,188). There is also diversity and variable levels of carbohydrate modifications demonstrated in the various isoforms of the catalytic domains of Rgp (41,60). This may partly account for the heterogeneity in the RgpA and RgpB isoforms.…”

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confidence: 99%

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

Sheets

Robles-Price²,

McKenzie³

et al. 2008

Front Biosci

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Porphyromonas gingivalis, a major periodontal pathogen, must acquire nutrients from host derived substrates, overcome oxidative stress and subvert the immune system. These activities can be coordinated via the gingipains which represent the most significant virulence factor produced by this organism. In the context of our contribution to this field, we will review the current understanding of gingipain biogenesis, glycosylation, and regulation, as well as discuss their role in oxidative stress resistance and apoptosis. We can postulate a model, in which gingipains may be part of the mechanism for P. gingivalis virulence. KeywordsPorphyromonas gingivalis; gingipains; apoptosis; caspase-independent apoptosis; oxidative stress; VimA; anoikis; N-cadherin; VE-cadherin; integrin β1; VimA; VimE; VimF; DNA repair; glycosylation; virulence; host cell survival; HRgpA; RgpB; Kgp; Review INTRODUCTIONP. gingivalis, a black-pigmented, Gram-negative anaerobe, is an important etiological agent of periodontal disease and is also linked to cardiovascular disease and other systemic diseases [reviewed in (43,103)]. The inflammatory nature of periodontal disease implies that innate host defense mechanisms play a vital role in limiting bacterial growth. During active infection including tissue invasion, toxic reactive oxygen metabolites (e.g. superoxides, hydrogen peroxide and hydroxyl radicals) are mostly generated by polymorphonuclear leukocytes and macrophages (27,29). In order to survive in the inflammatory environment of the periodontal pocket, the bacterium must not only obtain nutrients for growth, but also overcome oxidative stress and subvert the immune defense system. Coordinated regulation of these activities would be beneficial to the bacterium. While there is documented evidence of the response of P. gingivalis to environmental stimulus (56,117,126), one possible mechanism for coordination may occur via the gingipains produced by this bacterium. The presence of P. gingivalis in the periodontal pocket and the high levels of gingipain activity detected in gingival crevicular fluid could implicate a role for gingipains in the destruction of the highly vascular periodontal tissue. Protease-associated degradation of cell-cell adhesion proteins on epithelial and endothelial cells resulting in cell death will compromise tissue integrity and facilitate spreading of the bacterium. Furthermore, degradation of the immune response components will facilitate the survival of the organism. Together, these activities may also satisfy the nutritional requirements of the organism. Gingipain-dependent heme accumulation on the bacterium cell surface may also act as an "oxidative sink", thus, leading to protection against oxidative stress (191,193). We will discuss the role of the gingipains in the survival/pathogenicity of P. gingivalis and the unique vim (virulence modulating) locus that is involved in regulation of the gingipains. We will highlight some of our observations that are consistent with the hypothesis that the gingipain...

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Glycosylation of the Arg-gingipains of Porphyromonas gingivalis and Comparison with Glycoconjugate Structure and Synthesis in other Bacteria

Cited by 34 publications

References 0 publications

VimA is part of the maturation pathway for the major gingipains of Porphyromonas gingivalis W83

VimA is part of the maturation pathway for the major gingipains of Porphyromonas gingivalis W83

Selective Sorting of Cargo Proteins into Bacterial Membrane Vesicles

Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis

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