ArticleInfection and immunity2002
Attenuation of the virulence of Porphyromonas gingivalis by using a specific synthetic Kgp protease inhibitor.
Article in Infection and immunity, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 72 citations in OpenAlex.
- Transposase-Associated Variation nearPathogens (Basel, Switzerland) · 2026Article
- PorA of the Type IX Secretion Is a Ligand of the PorXY Two-Component Regulatory System in Porphyromonas gingivalis.Molecular microbiology · 2025Article
- Hemin availability induces coordinated DNA methylation and gene expression changes inmSystems · 2023Article
- The Murine Oral Metatranscriptome Reveals Microbial and Host Signatures of Periodontal Disease.Journal of dental research · 2023Article
- Local and Systemic Effects ofMicroorganisms · 2023Review
- Advances in novel therapeutic approaches for periodontal diseases.BMC oral health · 2022Review
- Molecular basis for avirulence of spontaneous variants of Porphyromonas gingivalis: Genomic analysis of strains W50, BE1 and BR1.Molecular oral microbiology · 2022Article
- Kgp DNA Vaccine Prevents Experimental Periodontitis.Oral health & preventive dentistry · 2021Article
- A PorX/PorY and σmSphere · 2021Article
- Inherently and Conditionally Essential Protein Catabolism Genes of Porphyromonas gingivalis.Trends in microbiology · 2021Review
- TheJournal of dental research · 2020Article
- Review
- Oxidative stress induced by Porphyromonas gingivalis lysate and nicotine in human periodontal ligament fibroblasts.Odontology · 2019Article
- A novel peptidic inhibitor derived from Streptococcus cristatus ArcA attenuates virulence potential of Porphyromonas gingivalis.Scientific reports · 2017Article
- Article
- Article
- Involvement of an Skp-Like Protein, PGN_0300, in the Type IX Secretion System of Porphyromonas gingivalis.Infection and immunity · 2016Article
- Article
- Non-conventional therapeutics for oral infections.Virulence · 2015Review
- Structure and mechanism of cysteine peptidase gingipain K (Kgp), a major virulence factor of Porphyromonas gingivalis in periodontitis.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Arg- and Lys-gingipains of Porphyromonas gingivalis are important virulence determinants in periodontal disease and may correspond to targets for immune- or drug-based treatment strategies. In this investigation we aimed to determine which of these enzymes represents the most promising molecular target for protease inhibitor-based therapy and to examine the effectiveness of the resultant compound in a murine virulence assay. Isogenic mutants with mutations in rgpA and rgpB (encoding Arg-gingipains) and in kgp (encoding Lys-gingipain) and a double mutant with mutations in rgpA and rgpB were prepared by using P. gingivalis W50. The virulence of these mutants indicated that Kgp is a promising drug target. Combinatorial chemistry was used to define the optimal substrate of Kgp, and from this information a specific slowly reversible inhibitor with a nanomolar K(i) was designed and synthesized. Growth of P. gingivalis W50 in the presence of this compound resembled the phenotype of the kgp isogenic mutant; in both instances bacterial colonies failed to form pigment on blood agar, and only poor growth was obtained in a defined medium containing albumin as the sole protein source. Furthermore, pretreatment of the wild-type organism with the Kgp inhibitor led to a significant reduction in virulence in the murine assay. These data emphasize the conclusion that Kgp is an important factor for both nutrition and virulence of P. gingivalis and that inhibitors of this enzyme may have therapeutic potential for the control of P. gingivalis infections. Protease inhibitors may be a potentially novel class of antimicrobial agents with relevance to the control of other bacterial pathogens.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.