Localized juvenile periodontitis (LJP) is the disease that occurs when bacteria accumulate on the junctional epithelium in the oral cavity. It was found in the middle of the last decade that Actinobacillus actinomycetemcomitans is the major causative agent of LJP and, more recently, as one of the microorganisms responsible for adult periodontitis. Periodontitis is the most prevalent chronic inflammatory diseases in humans, and it is major cause of tooth loss. It is evident that this dental pathogen grows actively and persists during the infectious process, which depends upon the ability of this microorganism to obtain growth-essential nutrients such as iron. Iron withholding by vertebrate hosts is an efficient mechanism against bacterial infections, and, thus bacteria must express efficient transport systems to acquire this essential nutrient to multiply during infection. There are indications that A. actinomycetemcomitans does not secrete siderophore compounds and it may acquire iron through periplasmic-binding protein-dependent transport systems. However, the genes and bacterial products involved in these processes and their role in virulence remain to be characterized. Therefore, the long-term objective of this application is the characterization of the mechanisms that A. actinomycetemcomitans uses to acquire iron and their participation in the pathogenesis of juvenile and adult periodontitis. In this proposal, the Principal Investigator addresses these goals through several approaches, combining methods used in classical and molecular bacterial genetics with molecular biology techniques designed to examine differential gene expression. The first specific aim involves a detailed genetic and molecular characterization of two potential iron periplasmic-transport systems, while the second specific aim focuses on the analysis of the expression of these systems in bacterial cells cultured in bacteriological media and in tissue culture flasks containing monolayers of human oral epithelial cells. The third specific aim proposes to determine the role of these potential iron transport systems in iron acquisition and the virulence of A. actinomycetemcomitans by creating and testing isogenic mutants. These proposed studies address an important and largely unexplored aspect of the pathogenesis caused by A. actinomycetemcomitans. Furthermore, these studies will lead to a better understanding of the nature of the interactions between the host and this pathogen during colonization and invasion of oral tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013657-02
Application #
6516603
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Lunsford, Dwayne
Project Start
2001-08-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$126,000
Indirect Cost
Name
Miami University Oxford
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
041065129
City
Oxford
State
OH
Country
United States
Zip Code
45056
Perry, Robert D; Bobrov, Alexander G; Kirillina, Olga et al. (2012) Yersinia pestis transition metal divalent cation transporters. Adv Exp Med Biol 954:267-79
Rhodes, Eric R; Menke, Sharon; Shoemaker, Christopher et al. (2007) Iron acquisition in the dental pathogen Actinobacillus actinomycetemcomitans: what does it use as a source and how does it get this essential metal? Biometals 20:365-77
Rhodes, Eric R; Shoemaker, Christopher J; Menke, Sharon M et al. (2007) Evaluation of different iron sources and their influence in biofilm formation by the dental pathogen Actinobacillus actinomycetemcomitans. J Med Microbiol 56:119-28
Rhodes, Eric R; Tomaras, Andrew P; McGillivary, Glen et al. (2005) Genetic and functional analyses of the Actinobacillus actinomycetemcomitans AfeABCD siderophore-independent iron acquisition system. Infect Immun 73:3758-63
Dorsey, Caleb W; Tomaras, Andrew P; Connerly, Pamela L et al. (2004) The siderophore-mediated iron acquisition systems of Acinetobacter baumannii ATCC 19606 and Vibrio anguillarum 775 are structurally and functionally related. Microbiology 150:3657-67
Tomaras, Andrew P; Dorsey, Caleb W; Edelmann, Richard E et al. (2003) Attachment to and biofilm formation on abiotic surfaces by Acinetobacter baumannii: involvement of a novel chaperone-usher pili assembly system. Microbiology 149:3473-84
Actis, L A; Rhodes, E R; Tomaras, A P (2003) Genetic and molecular characterization of a dental pathogen using genome-wide approaches. Adv Dent Res 17:95-9
Dorsey, Caleb W; Tolmasky, Marcelo E; Crosa, Jorge H et al. (2003) Genetic organization of an Acinetobacter baumannii chromosomal region harbouring genes related to siderophore biosynthesis and transport. Microbiology 149:1227-38
Dorsey, Caleb W; Tomaras, Andrew P; Actis, Luis A (2002) Genetic and phenotypic analysis of Acinetobacter baumannii insertion derivatives generated with a transposome system. Appl Environ Microbiol 68:6353-60