title: Tight-adherence genes of Actinobacillus actinomycetemcomitans are required for virulence in a rat model.
abstract: Actinobacillus actinomycetemcomitans is a Gram-negative coccobacillus that has been associated with localized aggressive periodontitis and infections of the heart, brain, and urinary tract. Wild-type clinical isolates have the remarkable ability to adhere tenaciously and nonspecifically to solid surfaces such as glass, plastic, and hydroxyapatite. Adherence by A. actinomycetemcomitans is mediated by the tight-adherence (tad) gene locus, which consists of 14 genes (flp-1-flp-2-tadV-rcpCAB-tadZABCDEFG). All but 2 of the genes have been shown to be required for the secretion and assembly of long, bundled Flp1 fibrils. To test whether the tad locus is required for colonization and disease, we developed a rat model for periodontal disease. To mimic the natural route of infection, Sprague-Dawley rats were inoculated orally by adding bacteria directly to their food for 8 days. After inoculation with wild-type or mutant strains defective in adherence (flp-1 and tadA), the rats were assessed for colonization of the oral cavity and pathogenesis. Wild-type A. actinomycetemcomitans was able to colonize and persist for at least 12 weeks in the oral cavity, elicit a humoral immune response, and cause significant bone loss in rats. In contrast, rats fed flp-1 or tadA mutant strains showed no bone loss and their immune responses were indistinguishable from those of the uninoculated controls. These results demonstrate the critical importance of the tad locus in the colonization and pathogenesis of A. actinomycetemcomitans.
authors.affiliation: Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Schreiner
authors.forename: Kathy
authors.initials: K
authors.lastname: Sinatra
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Kaplan
authors.forename: David
authors.initials: D
authors.lastname: Furgang
authors.forename: Scott C
authors.initials: SC
authors.lastname: Kachlany
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Planet
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Perez
authors.forename: David H
authors.initials: DH
authors.lastname: Figurski
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Fine
mesh_terms: D000189:Actinobacillus Infections / Q000209:etiology; D000251:Adenosine Triphosphatases / Q000235:genetics; D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D016301:Alveolar Bone Loss / Q000209:etiology; D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005798:Genes, Bacterial; D006801:Humans; D008297:Male; D008437:Maxilla / Q000473:pathology; D009154:Mutation; D010518:Periodontitis / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; C113731:Flp protein, bacteria; D000251:Adenosine Triphosphatases; C436966:TadA protein, Actinobacillus actinomycetemcomitans