Neisseria meningitidis expresses numerous adhesins that allow it to interact with diverse microenvironments within the host – resulting in asymptomatic nasopharyngeal colonization or invasive disease (sepsis/meningitis). The host receptors involved in these interactions are not fully elucidated, but are known to involve several carbohydrate structures (glycans). Investigating 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 the mechanisms by which N. meningitidis interacts with host cells.
Glycan arrays, with 364 glycans representative of those found on host cells, were probed with fluorescently labelled wild-type and mutant strains (each lacking a key outer membrane protein (OMP)) to identify the meningococcal glyco-interactome. Surface plasmon resonance, with recombinant proteins, was used to determine binding affinities.
Neisseria meningitidis wild-type bound 223 glycans, including blood group antigens, mucins, gangliosides and glycosaminoglycans. Some of these interactions were lost when key OMPs were deleted. The Opc adhesin mutant lost binding to glycosaminoglycans, including chondroitin sulphate, involved in adherence of several pathogens. The pili mutant lost binding to 56 or 61 structures, depending on the presence/absence of the capsule. Glyco-interactions of different meningococcal lipooligosaccharide (LOS) variants (L3, L8 immunotypes) were also investigated. The L3 variant (whole cells and purified LOS), uniquely bound 26 structures, while L8 only bound 5 structures.
These findings highlight the diverse glyco-interactions that may occur during different stages of meningococcal disease, which could be exploited for therapeutic development. Glycan structures vary between meningococcal niche(s), and/or between individuals, and the OMPs investigated undergo phase variation. As such, different bacterial-glycan interactions may be more relevant during certain stages of disease, i.e., nasopharyngeal colonisation versus sepsis or meningitis. Infection assays (epithelial colonization and human blood models) are underway to investigate the role of these glycan interactions in meningococcal disease.