Molecular Recognition Mechanisms of Meningococci: Identifying Receptor-Ligand Pairs Involved in Microbe-Host Interactions

Neisseria meningitidis is a human specific pathogen and resides primarily in the nasopharynx of its host. The molecular-recognition mechanisms that operate at the host-microbe interface to impart such precise host/tissue specificity are not fully defined. Given the host muco-cilliary clearance mechanisms, an obvious prerequisite for colonization is the ability of bacteria to make firm and rapid contact with the nasopharyngeal mucosa. The specificity for the niche indicates that one or more meningococcal adhesins have evolved an exquisite level of affinity for particular target molecules. They also exhibit considerable structural and phase modulations that aid in immune evasion. These properties have been exploited to derive distinct phenotypes for investigations on the mechanisms of adhesion. The in vitro investigations that use cell cultures of human origin or “humanized” cells (created by transfection of animal cells with human DNA) have identified a number of receptors targeted by meningococci. Detailed examination of the molecular mechanisms of bacterial ligation with the receptors will clarify the basis of tissue specificity and tropism and provide information that may lead to novel strategies to control the disease. We will describe some of the methods we have implemented over the years for such investigations.