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.

Opa Proteins
Neisseria gonorrhoeae and Neisseria meningitides 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, Opa_CEA, bind to carcinoembryonic antigen-like cellular adhesion molecules (CEACAMs), and the smaller class, Opa_HS, bind to two different receptors; the heparansulfate proteoglycan receptors (HSPGs) directly or indirectly to integrin receptors via fibronectin or vitronectin. The Columbus laboratory is determining the structure of Opa proteins and mapping their interactions to cognate receptors.
– Alison Dewald, Dan Fox, Ryan Lo, and Jacqueline Hodges

Inc Proteins
Chlamydiae are obligate intracellular bacteria that depend upon the metabolic activities of a host cell for survival and reproduction. These bacteria reside in membrane-bound vesicular niches termed inclusions that ultimately communicate with host exocytic trafficking to evade detection. Inclusion membrane proteins (Inc proteins) are a class of Chlamydiae proteins that reside in the inclusion membrane. To a large degree, the functions of these proteins are unknown. However, fusogenic studies have determined that IncA of C. trachomatis functions to facilitate homotypic fusion events between adjacent inclusions. The Columbus laboratory is investigating the structure of IncA.
– Ashley Keller and Tsiga Solomon