title: LuxS signaling in Porphyromonas gingivalis-host interactions.
abstract: Dental plaque is a multispecies biofilm in the oral cavity that significantly influences oral health. The presence of the oral anaerobic pathogen Porphyromonas gingivalis is an important determinant in the development of periodontitis. Direct and indirect interactions between P. gingivalis and the host play a major role in disease development. Transcriptome analysis recently revealed that P. gingivalis gene-expression is regulated by LuxS in both an AI-2-dependent and an AI-2 independent manner. However, little is known about the role of LuxS-signaling in P. gingivalis-host interactions. Here, we investigated the effect of a luxS mutation on the ability of P. gingivalis to induce an inflammatory response in human oral cells in vitro. Primary periodontal ligament (PDL) fibroblasts were challenged with P. gingivalis ΔluxS or the wild-type parental strain and gene-expression of pro-inflammatory mediators IL-1β, IL-6 and MCP-1 was determined by real-time PCR. The ability of P. gingivalis ΔluxS to induce an inflammatory response was severely impaired in PDL-fibroblasts. This phenotype could be restored by providing of LuxS in trans, but not by addition of the AI-2 precursor DPD. A similar phenomenon was observed in a previous transcriptome study showing that expression of PGN_0482 was reduced in the luxS mutant independently of AI-2. We therefore also analyzed the effect of a mutation in PGN_0482, which encodes an immuno-reactive, putative outer-membrane protein. Similar to P. gingivalis ΔluxS, the P. gingivalis Δ0482 mutant had an impaired ability to induce an inflammatory response in PDL fibroblasts. LuxS thus appears to influence the pro-inflammatory responses of host cells to P. gingivalis, likely through regulation of PGN_0482.
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), VU Free University and the University of Amsterdam, Gustav Mahlerlaan 3004, 1081 BT Amsterdam, The Netherlands. Electronic address: nienmail@gmail.com.
authors.forename: Nina
authors.initials: N
authors.lastname: Scheres
authors.affiliation: Department of Oral Immunology and Infectious Diseases, University of Louisville School of Dentistry, Louisville, KY 40202, United States.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Lamont
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), VU Free University and the University of Amsterdam, Gustav Mahlerlaan 3004, 1081 BT Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Crielaard
authors.affiliation: Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), VU Free University and the University of Amsterdam, Gustav Mahlerlaan 3004, 1081 BT Amsterdam, The Netherlands. Electronic address: b.krom@acta.nl.
authors.forename: Bastiaan P
authors.initials: BP
authors.lastname: Krom
mesh_terms: D000293:Adolescent; D000328:Adult; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D016866:Bacteroidaceae Infections / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D013437:Carbon-Sulfur Lyases / Q000235:genetics / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology; D005260:Female; D005347:Fibroblasts / Q000276:immunology / Q000382:microbiology; D015964:Gene Expression Regulation, Bacterial; D005891:Gingivitis / Q000235:genetics / Q000276:immunology / Q000382:microbiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008297:Male; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D001426:Bacterial Proteins; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D013437:Carbon-Sulfur Lyases; C117753:LuxS protein, Bacteria
keywords: Autoinducer-2; Inflammatory response; PGN_0482; Periodontal fibroblast; Porphyromonas gingivalis; Quorum sensing