Streptococci are important integral components of the microbial biofilm that is present on the surface of oral tissues and are intimately involved in the dynamic processes that govern the establishment, growth and control of this biofilm. Their interactions with salivary proteins are important for initiating bacterial colonization of oral tissues and their subsequent interactions with other oral microbes contribute to the maturation of plaque. Many of these reactions are mediated by a family of related streptococcal proteins collectively known as the antigen I/II polypeptides. However, the mechanisms defining antigen I/II interactions with human and bacterial components in the oral cavity and their relationships and contributions to oral diseases are not fully understood. The goals of this proposal are to understand how the function of antigen I/II proteins differ among species of oral streptococci, how the structure of the antigen I/II polypeptide influences its function, and how the structure and activities of antigen I/II proteins are affected by the oral environment. To accomplish these goals, the Principal Investigator will determine if the expression of multiple antigen I/II proteins by streptococci results in a tighter association of these organisms with oral tissues. He will correlate specific structural characteristics of different antigen I/II proteins with their functions. In addition, studies are proposed to determine if antigen I/II functions as a dimer and if the environment within the oral cavity affects antigen I/II function by influencing the stability of the dimer interface. An understanding of how antigen I/II contributes to the initiation and growth of the oral microbial biofilm will lead to a better understanding of how pathogenic organisms become established in the oral cavity and how minor structural differences that occur within related groups of proteins can dramatically influence their function. Finally, understanding the higher order structure of the antigen I/II proteins may lead to the development of broad spectrum anti-microbial agents that function by disrupting specific protein- protein interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE012750-03
Application #
6176026
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Program Officer
Mangan, Dennis F
Project Start
1998-09-30
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2001-07-31
Support Year
3
Fiscal Year
2000
Total Cost
$226,515
Indirect Cost
Name
University of Pennsylvania
Department
Biochemistry
Type
Schools of Dentistry
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Lamont, Richard J; El-Sabaeny, Azza; Park, Yoonsuk et al. (2002) Role of the Streptococcus gordonii SspB protein in the development of Porphyromonas gingivalis biofilms on streptococcal substrates. Microbiology 148:1627-36
Demuth, Donald R; Irvine, Douglas C (2002) Structural and functional variation within the alanine-rich repetitive domain of streptococcal antigen I/II. Infect Immun 70:6389-98
Demuth, D R; Irvine, D C; Costerton, J W et al. (2001) Discrete protein determinant directs the species-specific adherence of Porphyromonas gingivalis to oral streptococci. Infect Immun 69:5736-41
El-Sabaeny, A; Demuth, D R; Park, Y et al. (2000) Environmental conditions modulate the expression of the sspA and sspB genes in Streptococcus gordonii. Microb Pathog 29:101-13