The Host-Pathogen Interactions and Epicellular Lifestyle of Neisseria meningitidis

Abstract

Neisseria meningitidis is a gram-negative diplococcus and a transient commensal of the human nasopharynx. It shares and competes for this niche with a number of other Neisseria species including N. lactamica, N. cinerea and N. mucosa. Unlike these other members of the genus, N. meningitidis may become invasive, crossing the epithelium of the nasopharynx and entering the bloodstream, where it rapidly proliferates causing a syndrome known as Invasive Meningococcal Disease (IMD). IMD progresses rapidly to cause septic shock and meningitis and is often fatal despite aggressive antibiotic therapy. While many of the ways in which meningococci survive in the host environment have been well studied, recent insights into the interactions between N. meningitidis and the epithelial, serum, and endothelial environments have expanded our understanding of how IMD develops. This review seeks to incorporate recent work into the established model of pathogenesis. In particular, we focus on the competition that N. meningitidis faces in the nasopharynx from other Neisseria species, and how the genetic diversity of the meningococcus contributes to the wide range of inflammatory and pathogenic potentials observed among different lineages.

Variable disruption of epithelial monolayers by Neisseria meningitidis carriage isolates of the hypervirulent MenW cc11 and MenY cc23 lineages

“…Meningococci are frequent, asymptomatic colonizers of the human nasopharynx, but some lineages have a higher propensity to traverse the respiratory epithelium and cause invasive infections [2,5,7]. The high genetic similarity of carriage and disease isolates indicates that disease-causing attributes are either inherent properties of disease-causing strains or arise due to rapid within-host adaptive processes.…”

“… Neisseria meningitidis (the meningococcus, Nm) is a Gram-negative human pathogen that transiently colonizes the nasopharynx of 10–35 % of healthy individuals in the population [1, 2]. This ‘carriage’ state is a prerequisite for translocation of meningococci across the respiratory epithelium into the bloodstream and for systemic infections referred to as invasive meningococcal disease (IMD), including septicaemia and meningitis [3, 4].…”

“…A key stage of meningococcal carriage is attachment to, and formation of, microcolonies on mucosal surfaces [2,9]. Epithelial adhesion by meningococci is predominantly mediated by the type IV pilus and outer-membrane proteins (OMPs).…”

Meningococcal virulence in zebrafish embryos depends on capsule polysaccharide structure

“…This fits with the observation that nonencapsulated meningococci rarely cause invasive meningococcal disease and when this occurs, the patients have comorbidities such as complement deficiencies. The meningococcal capsule protects against killing by complement, while non-encapsulated meningococci are extremely sensitive to it (Mikucki et al, 2022). In this respect, the zebrafish embryo infection model reflects the human requirements for meningococcal infection.…”

“…The meningococcus has to overcome the host innate immune system to survive and multiply in the blood stream of the host (Lewis and Ram, 2020). This is illustrated by the observation that complement-deficient individuals are more susceptible to IMD (Mikucki et al, 2022). The meningococcal polysaccharide capsule is the most important virulence factor, through its ability to confer serum resistance (Tzeng et al, 2016).…”