Molecular basis of pathogenic bacterial-host interactions.

Bacterial pathogens enter host cells and wreak havoc on biological processes essential for viability, typically resulting in illness and death. Bacterial membrane proteins mediate the invasion and intracellular survival of these pathogens in human host cells. The aim of this research proposal is to investigate the structure and dynamics of the membrane proteins involved in pathogenesis.

The pathogens of focus are Neisseria gonorrhoeae (NG) and Neisseria meningitides (NM). Neisseriae are pathogenic, obligate, gram-negative bacteria responsible for a variety of diseases including meningococcal meningitis and gonorrhea. Subsequent to pili binding, opacity associated (Opa) proteins bind to host plasma membrane receptors and signal the loss of the pili and host actin reorganization, which facilitates endocytosis into the host cytoplasm. Different Opa proteins bind to various host receptors and are classified into two classes. The larger class, OpaCEA, bind to carcinoembryonic antigen-like cellular adhesion molecules (CEACAMs), and the smaller class, OpaHS, bind to two different receptors; the heparansulfate proteoglycan receptors (HSPGs) directly or indirectly to integrin receptors via fibronectin or vitronectin.