title: Autoinducer-2 and QseC control biofilm formation and in vivo virulence of Aggregatibacter actinomycetemcomitans.
abstract: Biofilm formation by the periodontal pathogen Aggregatibacter actinomycetemcomitans is dependent upon autoinducer-2 (AI-2)-mediated quorum sensing. However, the components that link the detection of the AI-2 signal to downstream gene expression have not been determined. One potential regulator is the QseBC two-component system, which is part of the AI-2-dependent response pathway that controls biofilm formation in Escherichia coli. Here we show that the expression of QseBC in A. actinomycetemcomitans is induced by AI-2 and that induction requires the AI-2 receptors, LsrB and/or RbsB. Additionally, inactivation of qseC resulted in reduced biofilm growth. Since the ability to grow in biofilms is essential for A. actinomycetemcomitans virulence, strains that were deficient in QseC or the AI-2 receptors were examined in an in vivo mouse model of periodontitis. The DeltaqseC mutant induced significantly less alveolar bone resorption than the wild-type strain (P < 0.02). Bone loss in animals infected with the DeltaqseC strain was similar to that in sham-infected animals. The DeltalsrB, DeltarbsB, and DeltalsrB DeltarbsB strains also induced significantly less alveolar bone resorption than the wild type (P < 0.03, P < 0.02, and P < 0.01, respectively). However, bone loss induced by a DeltaluxS strain was indistinguishable from that induced by the wild type, suggesting that AI-2 produced by indigenous microflora in the murine oral cavity may complement the DeltaluxS mutation. Together, these results suggest that the QseBC two-component system is part of the AI-2 regulon and may link the detection of AI-2 to the regulation of downstream cellular processes that are involved in biofilm formation and virulence of A. actinomycetemcomitans.
authors.affiliation: Research Group in Oral Health and Systemic Disease, University of Louisville School of Dentistry, Room 209, Louisville, Kentucky 40292, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Novak
authors.forename: HanJuan
authors.initials: H
authors.lastname: Shao
authors.forename: Carlo Amorin
authors.initials: CA
authors.lastname: Daep
authors.forename: Donald R
authors.initials: DR
authors.lastname: Demuth
mesh_terms: D000189:Actinobacillus Infections / Q000382:microbiology*; D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D000818:Animals; D018441:Biofilms / Q000254:growth & development*; D003773:Dental Plaque / Q000382:microbiology; D004195:Disease Models, Animal; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005798:Genes, Bacterial / Q000235:genetics; D006714:Homoserine / Q000031:analogs & derivatives* / Q000502:physiology; D007783:Lactones; D051379:Mice; D010518:Periodontitis / Q000382:microbiology; D053038:Quorum Sensing / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007783:Lactones; C091088:N-octanoylhomoserine lactone; D006714:Homoserine
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