Drexel University College of Medicine

Neisseria gonorrhoeae (Ng) is the second most common sexually transmitted bacterium and is responsible for an estimated 62 million newly acquired cases of gonorrhea globally each year.  Survival in the human host is greatly enhanced by the presence of the surface-expressed virulence determinant lipooligosaccharide (LOS) sialyltransferase (Lst), which catalyzes the transfer of sialic acid to the terminal galactose residue of LOS.  LOS sialylation inhibits antibody binding and complement deposition and promotes survival during respiratory burst in phagocytic cells.  However, sialylation also impedes intimate adhesion and invasion of the epithelium, suggesting a critical role for Lst regulation that is partially niche-dependent.

We have demonstrated that two separate factors, CrgA (a soluble LysR-type transcriptional regulator) and Rsp (an inner membrane-expressed one-component regulator), promote transcriptional repression of Lst during cell association.  Current studies are focused on determining the mechanism of action for these factors in order to ascertain how crosstalk between the bacterium and the host effects Lst repression and susceptibility to killing.