Abstract
Despite being the agent of life-threatening meningitis, Neisseria meningitidis is usually carried asymptomatically in the nasopharynx of humans and only occasionally causes disease. The genetic bases for virulence have not been entirely elucidated and the search for new virulence factors in this species is hampered by the lack of an animal model representative of the human disease. As an alternative strategy we employ a molecular epidemiological approach to establish a statistical association of a candidate virulence gene with disease in the human population. We examine the distribution of a previously-identified genetic element, a temperate bacteriophage, in 1288 meningococci isolated from cases of disease and asymptomatic carriage. The phage was over-represented in disease isolates from young adults indicating that it may contribute to invasive disease in this age group. Further statistical analysis indicated that between 20% and 45% of the pathogenic potential of the five most common disease-causing meningococcal groups was linked to the presence of the phage. In the absence of an animal model of human disease, this molecular epidemiological approach permitted the estimation of the influence of the candidate virulence factor. Such an approach is particularly valuable in the investigation of exclusively human diseases.
Highlights
Despite its notoriety as the causative agent of meningococcal disease, which kills an estimated 50,000 individuals worldwide annually [1], Neisseria meningitidis is a frequent asymptomatic coloniser of the human nasopharynx
Many meningococci belonging to clonal complexes that are not hyperinvasive are encapsulated and have iron acquisition sytems; pili are required for colonisation of the human nasopharynx whether or not this is followed by disease
Iron acquisition systems and type IV pili are probably necessary for pathogenesis, but while possession of each of these factors is necessary for invasive disease it is not sufficient
Summary
Despite its notoriety as the causative agent of meningococcal disease, which kills an estimated 50,000 individuals worldwide annually [1], Neisseria meningitidis is a frequent asymptomatic coloniser of the human nasopharynx. Analysis of results from multilocus enzyme electrophoresis (MLEE [2]) and multilocus sequence typing (MLST [3]) have demonstrated the existence of distinct phylogenetic groupings (termed lineages, or clonal complexes), a small number of which are consistently more likely to be isolated from patients than are others [4]. These are the socalled hyper-virulent, or hyperinvasive, clonal complexes [3], which are responsible for the large majority of meningococcal disease worldwide. The pathogenicity of Neisseria meningitidis is multifactorial and it is likely that many determinants important for the invasive phenotype remain to be discovered
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