The HA2 haemagglutinin domain of the lysine-specific gingipain (Kgp) of Porphyromonas gingivalis promotes μ-oxo bishaem formation from monomeric iron(III) protoporphyrin IX

Smalley, John W.; Birss, Andrew J.; Szmigielski, Borys; Potempa, Jan

doi:10.1099/mic.0.28835-0

Cited by 30 publications

(33 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The first indication of Kgp involvement in haem accumulation came from a key genetic study showing that kgp mutant colonies did not present the normal black-pigmentation phenotype owing to haem adsorption at the cell surface [59]. Subsequent work showed that both proteinases were responsible for the capture of haemoglobin, its degradation and release, and conversion of haem to m-oxo bishaem aggregates [60,61]. Most recently, gingipain and HmuY activities have been linked together in the release of haem from proteins degraded by gingipains and its capture by HmuY [62].…”

Section: Haesr Systemmentioning

confidence: 99%

Two-component signal transduction systems in oral bacteria

Mattos-Graner

Duncan²

2017

Journal of Oral Microbiology

View full text Add to dashboard Cite

We present an overview of how members of the oral microbiota respond to their environment by regulating gene expression through two-component signal transduction systems (TCSs) to support conditions compatible with homeostasis in oral biofilms or drive the equilibrium toward dysbiosis in response to environmental changes. Using studies on the sub-gingival Gram-negative anaerobe Porphyromonas gingivalis and Gram-positive streptococci as examples, we focus on the molecular mechanisms involved in activation of TCS and species specificities of TCS regulons.

show abstract

Section: Haesr Systemmentioning

confidence: 99%

Two-component signal transduction systems in oral bacteria

Mattos-Graner

Duncan²

2017

Journal of Oral Microbiology

View full text Add to dashboard Cite

show abstract

“…An important component of the heme acquisition system in P. gingivalis involves the gingipains (65,115,148). Recent reports suggest that gingipains Kgp and RgpA are the major proteases involved in hemin acquisition, binding and accumulation in P. gingivalis (24,42,115,163,186,192). This raises an important question as to whether this organism would be more susceptible to oxidative stress in the absence or reduction of this "oxidative sink" layer.…”

Section: Oxidative Stress Resistance: Antioxidant Enzymes and Hemin Amentioning

confidence: 96%

“…The bound heme can be involved in the catalytic destruction of the toxic oxygen derivative species (191). Since proteolytic activity in P. gingivalis is associated with heme accumulation (152) via the HA2 hemagglutinin domains of Arg-and Lysgingipains (192), it might be considered an important strategy for the organism to coordinate its oxidative stress and proteolytic activities. Under conditions of oxidative stress, there is an increased proportion of cell-bound gingipain (RgpA and Kgp) activity (45).…”

Section: Regulation Of Gingipain Biogenesis and Virulence In P Gingimentioning

confidence: 99%

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

Sheets

Robles-Price²,

McKenzie³

et al. 2008

Front Biosci

View full text Add to dashboard Cite

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...

show abstract

“…When growing on blood agar plates P. gingivalis colonies are initially white to creamy in colour, but turn dark red to black after 6-10 days [26]. The black pigmentation has been verified as an accumulation of iron (III) protoporphyrin IX in the form of the µ-oxo dimer [Fe(III)PPIX] 2 O on the bacterial cell surface [29]. Among the common laboratory strains and clinical isolates of P. gingivalis, strains W83, W12 and W50 are found to be more virulent than strains 381, HG66 and ATCC33277 [30].…”

Section: An Unusual Oral Pathogen Porphyromonas Gingivalismentioning

confidence: 99%

Gingipains fromPorphyromonas gingivalis— complex domain structures confer diverse functions

Li¹,

Collyer²

2011

European Journal of Microbiology and Immunology

View full text Add to dashboard Cite

Gingipains, a group of arginine or lysine specific cysteine proteinases (also known as RgpA, RgpB and Kgp), have been recognized as major virulence factors in Porphyromonas gingivalis. This bacterium is one of a handful of pathogens that cause chronic periodontitis. Gingipains are involved in adherence to and colonization of epithelial cells, haemagglutination and haemolysis of erythrocytes, disruption and manipulation of the inflammatory response, and the degradation of host proteins and tissues. RgpA and Kgp are multi-domain proteins composed of catalytic domains and haemagglutinin/adhesin (HA) regions. The structure of the HA regions have previously been defined by a gingipain domain structure hypothesis which is a set of putative domain boundaries derived from the sequences of fragments of these proteins extracted from the cell surface. However, multiple sequence alignments and hidden Markov models predict an alternative domain architecture for the HA regions of gingipains. In this alternate model, two or three repeats of the socalled "cleaved adhesin" domains (and one other undefined domain in some strains) are the modules which constitute the substructure of the HA regions. Recombinant forms of these putative cleaved adhesin domains are indeed stable folded protein modules and recently determined crystal structures support the hypothesis of a modular organisation of the HA region. Based on the observed K2 and K3 structures as well as multiple sequence alignments, it is proposed that all the cleaved adhesin domains in gingipains will share the same β-sandwich jelly roll fold. The new domain model of the structure for gingipains and the haemagglutinin (HagA) proteins of P. gingivalis will guide future functional studies of these virulence factors.Keywords: Porphyromonas gingivalis, cleaved adhesin, gingipain, haemagglutinin, lysine-and arginine-specific cysteine proteases *Corresponding author: Charles A. Collyer; Phone: +61 293512794; Fax: +61 293514726; E-mail: charles.collyer@sydney.edu.au high as 50% [23]. P. gingivalis is a non-motile Gram-negative anaerobic bacillus [18]. In contrast to other members of the genus Porphyromonas, many of which are able to grow on complex carbohydrates, P. gingivalis is asaccharolytic and reliant upon nitrogenous substrates such as proteins or peptides as nutrients and for metabolic energy [24][25][26]. P. gingivalis is able to produce a large amount of proteinases to degrade proteins from host or other microorganisms in order to meet its special nutritional requirements [5,18]. Importantly, this bacterium needs exogenous haem for growth due to the lack of a haem biosynthesis pathway [27][28]. P. gingivalis is mostly found in bleeding chronic periodontal lesions, where haemoglobin from ruptured erythrocytes provides a very convenient and abundant haem source. When growing on blood agar plates P. gingivalis colonies are initially white to creamy in colour, but turn dark red to black after 6-10 days [26]. The black pigmentation has been verified as an accumulation of iron (...

show abstract

The HA2 haemagglutinin domain of the lysine-specific gingipain (Kgp) of Porphyromonas gingivalis promotes μ-oxo bishaem formation from monomeric iron(III) protoporphyrin IX

Cited by 30 publications

References 47 publications

Two-component signal transduction systems in oral bacteria

Two-component signal transduction systems in oral bacteria

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

Gingipains fromPorphyromonas gingivalis— complex domain structures confer diverse functions

Contact Info

Product

Resources

About