Neisseria meningitidis, an exclusively human pathogen and commensal, poses a considerable public health threat. Despite the availability of effective antibiotics and several vaccines, N. meningitidis remains a leading cause of bacterial meningitis, with mortality rates as high as 10% and survivors often endure debilitating sequelae.
N. meningitidis expresses numerous adhesins that allow it to interact with diverse microenvironments within the host – resulting in asymptomatic nasopharyngeal colonization of the mucosal epithelia, as well as invasion and spread within the blood stream and infection of the meninges. On the host side, the receptors involved in these stages of infection are not fully elucidated, but are known to involve several carbohydrate structures (glycans). Understanding the glycobiology of N. meningitidis, i.e. elucidating the glycan-lectin interactions between meningococci and host cells, is important for a better understanding of meningococcal pathogenesis, and ultimately, improved meningococcal vaccine development.
We used glycan arrays, printed with 364 glycans that are representative of those found on host cell surfaces, as a screening tool to identify the glyco-interactome of N. meningitidis. N. meningitidis MC58 wild type bound a variety of glycans, including Blood Group Antigens, cancer associated antigens, mucin core glycans, gangliosides and glycosaminoglycans. We have also determined the glycan binding properties of a series of mutant strains lacking the major meningococcal outer membrane structures, in order to identify the lectins responsible for some of these interactions.
Affinity/kinetics studies (via surface plasmon resonance) and infection assays (using meningococcal epithelial cell colonization models and human blood models of sepsis) are now being performed to confirm specific glycan interactions, and determine their roles in meningococcal disease.