Genetics and evolution of Neisseria meningitidis: Importance for the epidemiology of meningococcal disease

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Abstract

Meningococcal disease is a life-threatening illness occurring worldwide with incidence rates varying from 1 to 1000 cases per 100 000. The causative organism, Neisseria meningitidis, is a normal commensal of humans. While strains associated with asymptomatic carriage are highly diverse, a few hyper-invasive genetic clones of the species may spread rapidly through human populations, resulting in countrywide epidemics of meningococcal meningitis. N. meningitidis fitness for spread and colonization is directly linked to the capability of the bacterium to change its genome and adapt to its environment, by means of a variety of genetic mechanisms. This review addresses some of the impacts of the evolutionary potential of N. meningitidis on the occurrence of meningococcal disease.

Section snippets

Introduction: the meningococcus, a human commensal

Neisseria meningitidis, the meningococcus, is a Gram-negative diplococcus bacterium, member of the family Neisseriaceae (Cimolai and Caugant, 2001). It is an obligate commensal of humans and the majority of people will at one time or another harbor the bacterium asymptomatically in the throat, a phenomenon known as carriage (Broome, 1986). N. meningitidis survives only very shortly in the environment; thus, transmission between hosts requires the spread of upper respiratory secretions from an

Meningococcal disease

Occasionally, shortly after the onset of colonization, N. meningitidis strains might penetrate the mucosal membrane and gain access to the bloodstream. Bacteria that are able to survive and multiply in the circulation may then cross the meninges and gain access to the cerebrospinal fluid. Of the various forms of meningococcal disease, the most common ones are meningitis, which may occur as epidemics, and severe sepsis with often a rapid fatal outcome (Brandtzæg and van Deuren, 2002). Despite

The bacterium and serological classification

A capsular polysaccharide, which is protecting the bacterium during the invasion process, is the outermost antigenic structure on the meningococcal surface and the primary target for mucosal and humoral immunity. Strains of N. meningitidis have been classified since the 1930s by serological typing based on antigenic properties of the capsular polysaccharide, which identifies the serogroup. Twelve serogroups are distinguished and chemically defined: A, B, C, 29E, H, I, K, L, W135, X, Y, and Z.

Genetic methods for the characterization of N. meningitidis

While serological typing methods have been useful for public health decisions in relation to disease control and vaccine development, they exhibit a number of limitations, which had made them inappropriate for epidemiological studies of meningococcal disease. Among these limitations, the most significant ones are: (1) incomplete coverage of typing reagents; (2) typing target not expressed in all isolates; and (3) poor correlation with genetic relatedness of isolates due to the high levels of

Genetic variation in housekeeping genes and population structure

There are two main factors that determine how different microbial organisms derived from a common ancestor are: the time elapsed since their divergence and their potential for evolutionary changes. The potential for evolution of bacteria depends upon the genetic mechanisms that they have available (mutation, recombination, inversion, DNA repair, etc.) and their respective rates as well as upon the structuring and the ecology of their populations. Bacteria that are able to incorporate foreign

Antigenic variation and virulence

In the presence of extensive recombination the persistence of clonal complexes suggests that some important selective forces are maintaining the structuring of the population of N. meningitidis. Factors such as virulence characteristics, transmissibility, and susceptibility of the human reservoir to specific strains or clonal groups will result in limiting the gene flow between meningococcal strains.

A prerequisite for an increased incidence of meningococcal disease in a population is the spread

Challenges for disease control

Even in parts of the world where state of the art treatment can be obtained, meningococcal disease continues to be a frightening disease with often a fatal outcome, because of its rapid onset and progression, particularly in case of sepsis. Effective prevention strategies relying on vaccination have therefore been the focus of much attention. Based on the importance of the capsule for pathogenesis and immunity, capsular polysaccharide vaccines were developed and introduced in the 1970s and

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