Haemin binding as a factor in the virulence of Porphyromonas gingivalis

Smalley, John W.

doi:10.1016/0378-1097(96)00209-1

Cited by 13 publications

(27 citation statements)

References 3 publications

(6 reference statements)

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“…Such redundancy in hemin uptake and storage mechanisms in P. gingivalis may facilitate tight control and ensure adaptability to (37), while culture in excess hemin enhances the virulence of P. gingivalis (46). Moreover, a mutant of P. gingivalis that has diminished hemin binding displays reduced virulence (67). While there is general agreement that the virulence factors of P. gingivalis that are affected by hemin levels include hemin binding and protease production, the nature of this regulation is less clear.…”

Section: Discussionmentioning

confidence: 99%

LuxS Involvement in the Regulation of Genes Coding for Hemin and Iron Acquisition Systems inPorphyromonas gingivalis

et al. 2006

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The periodontal pathogen Porphyromonas gingivalis employs a variety of mechanisms for the uptake of hemin and inorganic iron. Previous work demonstrated that hemin uptake in P. gingivalis may be controlled by LuxS-mediated signaling. In the present study, the expression of genes involved in hemin and iron uptake was determined in parent and luxS mutant strains by quantitative real-time reverse transcription-PCR. Compared to the parental strain, the luxS mutant showed reduced levels of transcription of genes coding for the TonB-linked hemin binding protein Tlr and the lysine-specific protease Kgp, which can degrade host hemecontaining proteins. In contrast, there was up-regulation of the genes for another TonB-linked hemin binding protein, HmuR; a hemin binding lipoprotein, FetB; a Fe 2؉ ion transport protein, FeoB1; and the iron storage protein ferritin. Differential expression of these genes in the luxS mutant was maximal in early-exponential phase, which corresponded with peak expression of luxS and AI-2 signal activity. Complementation of the luxS mutation with wild-type luxS in trans rescued expression of hmuR. Mutation of the GppX two-component signal transduction pathway caused an increase in expression of luxS along with tlr and lower levels of message for hmuR. Moreover, expression of hmuR was repressed, and expression of tlr stimulated, when the luxS mutant was incubated with AI-2 partially purified from the culture supernatant of wild-type cells. A phenotypic outcome of the altered expression of genes involved in hemin uptake was impairment of growth of the luxS mutant in hemin-depleted medium. The results demonstrate a role of LuxS/AI-2 in the regulation of hemin and iron acquisition pathways in P. gingivalis and reveal a novel control pathway for luxS expression.

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Section: Discussionmentioning

confidence: 99%

LuxS Involvement in the Regulation of Genes Coding for Hemin and Iron Acquisition Systems inPorphyromonas gingivalis

et al. 2006

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“…gingivalis binds W-oxo bishaem and monomeric forms of iron(III) protoporphyrin IX [9,10] which are both present in the haem pigment [1] and have`catalase' activity [6]. gingivalis binds W-oxo bishaem and monomeric forms of iron(III) protoporphyrin IX [9,10] which are both present in the haem pigment [1] and have`catalase' activity [6].…”

Section: Reaction Of W-oxo Bishaem and Cells With Hydrogen Peroxidementioning

confidence: 99%

“…This haem species has been previously referred to as W-oxo dimers and as W-oxo oligomers, neither of which is strictly accurate. Given the ability of P. gingivalis to bind both monomeric iron protoporphyrin IX and its W-oxo bishaem [1,9,10], and the subsequent accumula-tion of large quantities of W-oxo bishaem into its pigment from blood [1], it may be reasoned that it would endure exposure to hydrogen peroxide. During pigment formation, W-oxo bishaem is generated through the reaction of haemoglobin-derived iron(II) protoporphyrin IX monomers and environmental oxygen [1].…”

Section: Introductionmentioning

confidence: 99%

The periodontal pathogen Porphyromonas gingivalis harnesses the chemistry of the μ-oxo bishaem of iron protoporphyrin IX to protect against hydrogen peroxide

Smalley¹

2000

FEMS Microbiology Letters

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The major haem component in the black pigment of Porphyromonas gingivalis is the μ‐oxo bishaem of iron protoporphyrin IX and formation and cell‐surface binding of this haem species is proposed as an extracellular buffer against reactive oxidants [Smalley, J.W. et al. (1998) Biochem. J. 331, 681–685]. P. gingivalis cells grown in the presence of the μ‐oxo bishaem were protected against H2O2 compared to control cells grown without it. When added to the growth medium, soluble μ‐oxo bishaem inactivated H2O2 and supported cell growth. Cells carrying a surface layer of μ‐oxo bishaem were less susceptible to peroxidation by H2O2. Cell‐surface haems were slowly destroyed during reaction with H2O2. Binding of μ‐oxo bishaem by P. gingivalis may aid survival during neutrophil attack through inactivation of hydrogen peroxide.

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“…P. gingivalis forms black-pigmented colonies on blood agar plates. Colonial pigmentation is caused by accumulation of -oxo heme dimer on the cell surface (58). Nonpigmented mutants of P. gingivalis have been isolated and characterized by a number of researchers (5,17,51,56,(62)(63)(64).…”

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confidence: 99%

APorphyromonas gingivalisMutant Defective in a Putative Glycosyltransferase Exhibits Defective Biosynthesis of the Polysaccharide Portions of Lipopolysaccharide, Decreased Gingipain Activities, Strong Autoaggregation, and Increased Biofilm Formation

et al. 2010

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The Gram-negative anaerobic bacterium Porphyromonas gingivalis is a major pathogen in periodontal disease, one of the biofilm-caused infectious diseases. The bacterium possesses potential virulence factors, including fimbriae, proteinases, hemagglutinin, lipopolysaccharide (LPS), and outer membrane vesicles, and some of these factors are associated with biofilm formation; however, the precise mechanism of biofilm formation is still unknown. Colonial pigmentation of the bacterium on blood agar plates is related to its virulence. In this study, we isolated a nonpigmented mutant that had an insertion mutation within the new gene Porphyromonas gingivalis is a major pathogen in severe forms of periodontal disease and refractory periapical perodontitis (28,39). This Gram-negative anaerobic bacterium possesses several virulence factors, including fimbriae, proteinases, hemagglutinin, lipopolysaccharide (LPS), and outer membrane vesicles (7,13,16,27). P. gingivalis forms black-pigmented colonies on blood agar plates. Colonial pigmentation is caused by accumulation of -oxo heme dimer on the cell surface (58). Nonpigmented mutants of P. gingivalis have been isolated and characterized by a number of researchers (5,17,51,56,(62)(63)(64). Colonial pigmentation on blood agar plates has been shown to be linked with hemagglutination and activities of major proteinases, Arggingipain (Rgp) and Lys-gingipain (Kgp), and other virulence factors, suggesting that colonial pigmentation is associated with the presence of gingipain-adhesin complexes on the cell surface (3,11,60).Pigmentation-related genes that have been characterized are classified into three categories: gene expression, membrane translocation, and surface attachment of gingipain-adhesin complexes (51). Gingipain-adhesin complexes comprise Rgp and Kgp proteinases encoded by rgpA, rgpB, and kgp and adhesins encoded by rgpA, kgp, and hagA. kgp single and rgpA rgpB kgp triple mutants form less-and nonpigmented colonies, respectively, whereas an rgpA rgpB double mutant forms pigmented colonies (42, 55). Smalley et al. (59) found that Rgp activity is crucial for converting oxyhemoglobin into the methemoglobin form, which is rendered more susceptible to Kgp degradation for the eventual release of iron(III) protoporphyrin IX and production of -oxo heme dimer. A defect in membrane translocation of gingipain-adhesin complexes causes nonpigmentation. The three genes porT, sov, and PG0027, mutants of which exhibit nonpigmentation, have been reported to be involved in membrane translocation of gingipain-adhesin complexes (18,49,53). High-molecularweight forms of Rgp, Kgp, and adhesins accumulate in the periplasmic space of those mutants (49,53). Very recently, we found a novel protein secretion system, the Por secretion system (PorSS), mediating secretion for gingipain-adhesin complexes, and the porK, porL, porM, porN, porP, porQ, porU, porW, porX, and porY genes have been added to this category (52).

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Haemin binding as a factor in the virulence of Porphyromonas gingivalis

Cited by 13 publications

References 3 publications

LuxS Involvement in the Regulation of Genes Coding for Hemin and Iron Acquisition Systems inPorphyromonas gingivalis

LuxS Involvement in the Regulation of Genes Coding for Hemin and Iron Acquisition Systems inPorphyromonas gingivalis

The periodontal pathogen Porphyromonas gingivalis harnesses the chemistry of the μ-oxo bishaem of iron protoporphyrin IX to protect against hydrogen peroxide

APorphyromonas gingivalisMutant Defective in a Putative Glycosyltransferase Exhibits Defective Biosynthesis of the Polysaccharide Portions of Lipopolysaccharide, Decreased Gingipain Activities, Strong Autoaggregation, and Increased Biofilm Formation

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