Importance of biofilm formation and dipeptidyl peptidase IV for the pathogenicity of clinical<i>Porphyromonas gingivalis</i>isolates

Clais, Sofie; Boulet, Gaëlle; Kerstens, Monique; Horemans, Tessa; Teughels, Wim; Quirynen, Marc; Lanckacker, Ellen; Meester, Ingrid De; Lambeir, Anne‐Marie; Delputte, Peter; Maes, Louis; Cos, Paul

doi:10.1111/2049-632x.12156

Cited by 23 publications

(22 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results of the screening show an overlap between the pharmacophores of pgDPP4 and DPP9 with respect to the azide and the P2 component. The best P2 residues are large, often with a nitrogen atom on a carbon spacer and substituted with bulky or aromatic groups (16,18 in Table 2 and 69, 72, 73 in Table S2). The most likely explanation is that they bind specifically in the S2-extensive pocket which is deeper than in hDPP4 and has a different charge distribution (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

“…Transfection with recombinant pgDPP4 restored virulence, while a catalytically impaired DPP4 only partially restored the wild type phenotype [15]. Moreover, clinical isolates of P. gingivalis strains with high DPP4 expression had a higher capacity for biofilm formation and were more infective in a mouse abscess model [16]. pgDPP4 belongs to the same family of proteases (prolyl oligopeptidase family, S9 clanB, MEROPS database) as human DPP4 (hDPP4), with which it shares 32% amino acid sequence identity.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling

Rea

Elzen

Winter

et al. 2017

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

The Gram-negative anaerobe Porphyromonas gingivalis is associated with chronic periodontitis. Clinical isolates of P. gingivalis strains with high dipeptidyl peptidase 4 (DPP4) expression also had a high capacity for biofilm formation and were more infective. The X-ray crystal structure of P. gingivalis DPP4 was solved at 2.2 Å resolution. Despite a sequence identity of 32%, the overall structure of the dimer was conserved between P. gingivalis DPP4 and mammalian orthologues. The structures of the substrate binding sites were also conserved, except for the region called S2-extensive, which is exploited by specific human DPP4 inhibitors currently used as antidiabetic drugs. Screening of a collection of 450 compounds as inhibitors revealed a structure-activity relationship that mimics in part that of mammalian DPP9. The functional similarity between human and bacterial DPP4 was confirmed using 124 potential peptide substrates.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling

Rea

Elzen

Winter

et al. 2017

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…As a result of a complex well‐organized structure, bacteria embedded in biofilm is 1000 times more resistant to antibiotic therapy compared to planktonic bacteria . Additionally, studies have shown that biofilm formation may enhance virulence of certain pathogenic bacteria like P. gingivais , S. mitis, F. nucleatum, A. viscosus, A. actinomycetemcomitans, and V. parvula …”

Section: Introductionmentioning

confidence: 99%

Inhibition of multi‐species oral biofilm by bromide doped bioactive glass

Galárraga-Vinueza

Passoni

et al. 2017

J Biomedical Materials Res

View full text Add to dashboard Cite

Bioactive glass is an attractive biomaterial that has shown excellent osteogenic and angiogenic effects for oral bone repairing procedures. However, anti-biofilm potential related to such biomaterial has not been completely validated, mainly against multi-species biofilms involved in early tissue infections. The aim of the present study was to evaluate the anti-biofilm effect of 58 S bioactive glass embedding calcium bromide compounds at different concentrations. Bioactive glass free or containing 5, or 10 wt % CaBr was synthesized by alkali sol-gel method and then characterized by physco-chemical analyses and scanning electron microscopy (SEM). Then, samples were tested by microbiological assays using optical density, real time q-PCR, and SEM. Bioactive glass particles showed accurate chemical composition and an angular shape with a bimodal size distribution ranging from 0.6 to 110 µm. The mean particle size was around 29 µm. Anti-biofilm effect was recorded for 5 wt % CaBr -doped bioactive glass against S. mitis, V. parvula, P. gingivais, S. gordoni, A. viscosus, F, nucleatum, P. gingivais. F. nucleatum, and P. gingivalis. Such species are involved in the biofilm structure related to infections on hard and soft tissues in the oral cavity. The incorporation of calcium bromide into bioactive glass can be a strategy to enhance the anti-biofilm potential of bioactive glasses for bone healing and infection treatment. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1994-2003, 2017.

show abstract

“…P. gingivalis DPP4 also hydrolyzes biologically active peptides that include substance P, fibrin inhibitory peptide, and β-casomorphin [19], and binds to fibronectin, thus it mediates bacterial adhesion to host cells [43]. A recent study also demonstrated that DPP4 was closely associated with biofilm formation in a murine subcutaneous abscess model [44].…”

Section: Peptidases Involved In Degradation Of Extracellular Proteinamentioning

confidence: 99%

“…In addition, DPP4 is involved in biofilm formation by P. gingivalis , which is closely related to bacterial virulence [44]. Hence, it is reasonable to postulate that other DPPs also contribute to biofilm formation and mixed-species colonization in subgingival plaque.…”

Section: Exopeptidases As Potential Virulence Factors Of P Gingivalismentioning

confidence: 99%

Exopeptidases and gingipains in Porphyromonas gingivalis as prerequisites for its amino acid metabolism

Nemoto

Ohara‐Nemoto

2016

Japanese Dental Science Review

View full text Add to dashboard Cite

SummaryPorphyromonas gingivalis, an asaccharolytic bacterium, utilizes amino acids as energy and carbon sources. Since amino acids are incorporated into the bacterial cells mainly as di- and tri-peptides, exopeptidases including dipeptidyl-peptidase (DPP) and tripeptidyl-peptidase are considered to be prerequisite components for their metabolism. We recently discovered DPP11, DPP5, and acylpeptidyl oligopeptidase in addition to previously reported DPP4, DPP7, and prolyl tripeptidyl peptidase A. DPP11 is a novel enzyme specific for acidic P1 residues (Asp and Glu) and distributed ubiquitously in eubacteria, while DPP5 is preferential for the hydrophobic P1 residue and the first entity identified in prokaryotes. Recently, acylpeptidyl oligopeptidase with a preference for hydrophobic P1 residues was found to release N-terminally blocked di- and tri-peptides. Furthermore, we also demonstrated that gingipains R and K contribute to P1-basic dipeptide production. These observations implicate that most, if not all, combinations of di- and tri-peptides are produced from extracellular oligopeptides even with an N-terminal modification. Here, we review P. gingivalis exopeptidases mainly in regard to their enzymatic characteristics. These exopeptidases with various substrate specificities benefit P. gingivalis for obtaining energy and carbon sources from the nutritionally limited subgingival environment.

show abstract

Importance of biofilm formation and dipeptidyl peptidase IV for the pathogenicity of clinicalPorphyromonas gingivalisisolates

Cited by 23 publications

References 23 publications

Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling

Crystal structure of Porphyromonas gingivalis dipeptidyl peptidase 4 and structure-activity relationships based on inhibitor profiling

Inhibition of multi‐species oral biofilm by bromide doped bioactive glass

Exopeptidases and gingipains in Porphyromonas gingivalis as prerequisites for its amino acid metabolism

Contact Info

Product

Resources

About