Bacterial attachment to host tissue is a critical first step in a process that may lead to clinically manifested infections. A bacterial infection can be regarded as a battle between the microbe and the host. This primary campaign starts with the bacteria's attempt to adhere and colonize the host. It is here that the surface components on bacteria play an important role. In Staphyloccocous aureus, the ligand-binding regions of all the surface proteins utilize a conserved DEv-IgG fold to bind to various extracellular matrix molecules through modification of residues and orientation of domains. We hypothesize that every bacterial species has developed its own system of adherence through a definitive adherence-motif. To address this hypothesis, we propose to identify the salivary agglutinin glycoprotein (SAG) adherence motif of Antigen l/ll (Agl/ll), a surface protein adhesin of Streptococcus mutans that is a known etiological agent of dental caries. The means by which Agl/ll interacts with SAG is now known to be mediated through gp340, a glycoprotein that contains scavenger receptor cystein rich (SRCR) domains. To identify the adherence-motif specifically, we will: 1) Determine the crystal structure of the AVP region of Agl/ll; 2) Map and characterize the interaction between the Agl/ll domains and gp340 domains; and finally 3) Create an Agl/ll-gp340 binding model and identify the binding-motif. The identification of the SAG adherence-motif of Agl/ll will facilitate structure-based drug design of either a small molecule or a peptide inhibitor for use in anti-infection therapy or for development of caries vaccine candidates. ? ? ?
