Actinobacillus actinomycetemcomitans (Aa) is a non-motile, Gram-negative facultative coccobacillus, which colonizes the human oral cavity and upper respiratory tract. Overwhelming microbial, immunological and clinical evidence implicates Aa in the pathogenesis of localized juvenile periodontitis and cases of rapid and refractory periodontal disease. This pathogen has been associated with other serious human infections such as endocarditis, soft tissue abscesses, and more recently cardiovascular disease. The periodontium has been implicated as the reservoir of these extraoral infections, although little is known about the mechanisms this pathogen utilizes to infiltrate and disseminate in tissues. The invasion into epithelial cells in vitro is well established and this periodontopathogen has been localized inside epithelial cells and found in sub epithelial cell layers in tissue biopsy from infected individuals. Our laboratory has demonstrated that Aa utilizes microtubules for intracellular trafficking and exit from epithelial cells. The data suggest that microtubules play a critical role in the spread and movement of Aa and provide the first evidence that host cell dispersion of an intracellular pathogen may involve the usurpation of microtubules. To further understand this unique interaction, we propose to 1) identify and characterize the bacterial macromolecule(s) that are involved in the interaction with microtubules and 2) characterize the component(s) of the epithelial cell microtubule asters that interact with Aa. The identification of these components will be important in understanding the processes that this pathogen uses to survive in the oral cavity and disperse into deeper tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE009760-11A1
Application #
6573141
Study Section
Special Emphasis Panel (ZRG1-OBM-1 (01))
Program Officer
Mangan, Dennis F
Project Start
1992-03-01
Project End
2007-11-30
Budget Start
2003-02-01
Budget End
2003-11-30
Support Year
11
Fiscal Year
2003
Total Cost
$378,750
Indirect Cost
Name
University of Vermont & St Agric College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
066811191
City
Burlington
State
VT
Country
United States
Zip Code
05405
Tang, Gaoyan; Mintz, Keith P (2010) Glycosylation of the collagen adhesin EmaA of Aggregatibacter actinomycetemcomitans is dependent upon the lipopolysaccharide biosynthetic pathway. J Bacteriol 192:1395-404
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Tang, Gaoyan; Kitten, Todd; Munro, Cindy L et al. (2008) EmaA, a potential virulence determinant of Aggregatibacter actinomycetemcomitans in infective endocarditis. Infect Immun 76:2316-24
Tang, Gaoyan; Ruiz, Teresa; Barrantes-Reynolds, Ramiro et al. (2007) Molecular heterogeneity of EmaA, an oligomeric autotransporter adhesin of Aggregatibacter (Actinobacillus) actinomycetemcomitans. Microbiology 153:2447-57
Ruiz, Teresa; Lenox, Christopher; Radermacher, Michael et al. (2006) Novel surface structures are associated with the adhesion of Actinobacillus actinomycetemcomitans to collagen. Infect Immun 74:6163-70
Wu, H; Lippmann, J E; Oza, J P et al. (2006) Inactivation of DNA adenine methyltransferase alters virulence factors in Actinobacillus actinomycetemcomitans. Oral Microbiol Immunol 21:238-44
Rose, John E; Meyer, Diane H; Fives-Taylor, Paula M (2003) Aae, an autotransporter involved in adhesion of Actinobacillus actinomycetemcomitans to epithelial cells. Infect Immun 71:2384-93
Mintz, Keith P; Moskovitz, Jackob; Wu, Hui et al. (2002) Peptide methionine sulfoxide reductase (MsrA) is not a major virulence determinant for the oral pathogen Actinobacillus actinomycetemcomitans. Microbiology 148:3695-703
Mintz, Keith P; Brissette, Catherine; Fives-Taylor, Paula M (2002) A recombinase A-deficient strain of Actinobacillus actinomycetemcomitans constructed by insertional mutagenesis using a mobilizable plasmid. FEMS Microbiol Lett 206:87-92
Liu, Bing; Rayment, Sean A; Soares, Rodrigo V et al. (2002) Interaction of human salivary mucin MG2, its recombinant N-terminal region and a synthetic peptide with Actinobacillus actinomycetemcomitans. J Periodontal Res 37:416-24

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