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Mapping the epithelial-cell-binding domain of the Aggregatibacter actinomycetemcomitans autotransporter adhesin Aae

By Daniel H. Fine, Jeffrey B. Kaplan, David Furgang, Maribasappa Karched, Kabilan Velliyagounder and Gang Yue


The Gram-negative periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) binds selectively to buccal epithelial cells (BECs) of human and Old World primates by means of the outer-membrane autotransporter protein Aae. We speculated that the exposed N-terminal portion of the passenger domain of Aae would mediate binding to BECs. By using a series of plasmids that express full-length or truncated Aae proteins in Escherichia coli, we found that the BEC-binding domain of Aae was located in the N-terminal surface-exposed region of the protein, specifically in the region spanning amino acids 201–284 just upstream of the repeat region within the passenger domain. Peptides corresponding to amino acids 201–221, 222–238 and 201–240 were synthesized and tested for their ability to reduce Aae-mediated binding to BECs based on results obtained with truncated Aae proteins expressed in E. coli. BEC-binding of E. coli expressing Aae was reduced by as much as 50 % by pre-treatment of BECs with a 40-mer peptide (201–240; P40). Aae was also shown to mediate binding to cultured human epithelial keratinocytes (TW2.6), OBA9 and TERT, and endothelial (HUVEC) cells. Pre-treatment of epithelial cells with P40 resulted in a dose-dependent reduction in binding and reduced the binding of both full-length and truncated Aae proteins expressed in E. coli, as well as Aae expressed in Aa. Fluorescently labelled P40 peptides reacted in a dose-dependent manner with BEC receptors. We propose that these proof-of-principle experiments demonstrate that peptides can be designed to interfere with Aa binding mediated by host-cell receptors specific for Aae adhesins

Topics: Microbial Pathogenicity
Publisher: Society for General Microbiology
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Provided by: PubMed Central
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    1. (2007). A second Aggregatibacter actinomycetemcomitans autotransporter adhesin that exhibits specificity for buccal epithelial cells of humans and Old World primates.
    2. (2003). Aae, an autotransporter involved in adhesion of Actinobacillus actinomycetemcomitans to epithelial cells.
    3. (1983). Adherence of group A streptococci to fibronectin on oral epithelial cells.
    4. (1975). Adhesion of enteropathogenic Escherichia coli to pig intestinal brush borders:theexistenceoftwopigphenotypes.JMe dM ic ro bi ol8,405–411.
    5. (2007). Aggregatibacter actinomycetemcomitans and its relationship to initiation of localized aggressive periodontitis: a longitudinal cohort study of initially healthy adolescents.
    6. (1981). Bacterial adherence: adhesin–receptor interactions mediating the attachment of bacteria to mucosal surfaces.
    7. (1987). Bacterial adherence: the attachment of group A streptococci to mucosal surfaces. Rev Infect Dis 9,
    8. (2007). Establishment and characterization of a tumorigenic cell line from areca quid and tobacco smoke-associated buccal carcinoma.
    9. (2000). How we got attached to Actinobacillus actinomycetemcomitans:a model for infectious diseases. Periodontol
    10. (2005). Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis.
    11. (2000). Identification of periodontal pathogens in atheromatous plaques.
    12. (2002). Identification of six major outer membrane proteins from Actinobacillus actinomycetemcomitans.
    13. (2001). Intracellular Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in A. actinomycetemcomitans autotransporter adhesin 3419buccal epithelial cells collected from human subjects.
    14. (2000). Invasion of human vascular endothelial cells by Actinobacillus actinomycetemcomitans via the receptor for platelet-activating factor.
    15. (1996). Natural distribution of oral Actinobacillus actinomycetemcomitans in young men with minimal periodontal disease.
    16. other authors (2003). Outer membrane protein 100, a versatile virulence factor of Actinobacillus actinomycetemcomitans.
    17. other authors (2004). Human gingival epithelial cells produce chemotactic factors interleukin-8 and monocyte chemoattractant protein-1 after stimulation with Porphyromonas gingivalis via Toll-like receptor 2.
    18. (1999). Phenotypic variation in Actinobacillus actinomycetemcomitans during laboratory growth: implications for virulence.
    19. (1996). Potential diagnostic value of sampling oral mucosal surfaces for Actinobacillus acintomycetemcomitans in young adults.
    20. (1979). Prevention of colonization of the urinary tract of mice with Escherichia coli by blocking of bacterial adherence with methyl a-D-mannopyranoside.
    21. (2008). Risk of aggressive periodontitis in adolescent carriers of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans in Morocco: a prospective longitudinal cohort study.
    22. Species specificity of in vitro Escherichia coli adherence to host intestinal cell membranes and its correlation with in vivo colonization and infectivity.
    23. (1976). Studies of the microbiology of periodontosis.
    24. The Actinobacillus actinomycetemcomitans autotransporter adhesin Aae exhibits specificity for buccal epithelial cells from humans and Old World primates.
    25. (1998). The great escape: structure and function of the autotransporter proteins.
    26. (1976). The predominant cultivable organisms in juvenile periodontitis.
    27. (2000). Treatment of acute otitis media with an antiadhesive oligosaccharide: a randomized, doubleblind, placebo-controlled trial.
    28. (2004). Type V protein secretion pathway: the autotransporter story.
    29. (2000). Virulence factors of Actinobacillus actinomycetemcomitans. Periodontol
    30. (2001). Virulence functions of autotransporter proteins.

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