The specific aims of this application will be to continue studies to define molecular and biochemical mechanisms involved in chlamydial-specific interactions with mammalian host cells. The aims are derived from that demonstrated a novel and essential role for glycoaminoglycan-mediated chlamydial attachment and invasion of host cells. The hypothesis is that chlamydiae attach to host cells by a trimolecular complex in which heparin sulfate-like glycosaminoglycan bridges lectin like acceptors on chlamydia and heparin sulfate receptors on the mammalian host cell. This interaction elicits receptor mediated endocytosis of the infectious organisms. A molecular understanding of attachment and entry will provide a rational foundation for the study of other important microbiological characteristics such as inhibition of lysosomal fusion, EB-RB differentiation, and persistence of infection. The specific aims are: 1) Molecular characterization of the glycosaminoglycan ligand (adhesin); 2) Characterize receptor-mediated endocytic pathway for host cell entry, 3) Identify and characterize the chlamydia glycosaminoglycan acceptor; and 4) Identify and characterize the mammalian host cell glycosaminoglycan receptor.