N.Meningitidis

N.Meningitidis is a small [blank_start]encapsulated[blank_end] Gram-[blank_start]negative[blank_end] [blank_start]diplococcus[blank_end]. It is carried in the [blank_start]nasopharynx[blank_end] by up to [blank_start]40[blank_end]% of individuals in closed communities and can cause septicaemia and meningitis in a minority of hosts. The organism is aerobic, [blank_start]catalase negative[blank_end], oxidase positive and non-motile. [blank_start]Second[blank_end] most common cause (behind S. pneumoniae) of community-acquired meningitis in previously healthy adults; swift progression from good health to life-threatening disease. Humans are the only [blank_start]natural host[blank_end]s and the organisms are transmitted by [blank_start]airborne droplets[blank_end]. They colonize the nasopharynx and become [blank_start]transient flora[blank_end] of the upper respiratory tract. From the nasopharynx, the organism can enter the bloodstream and spread to meninges or cause meningococcemia. N. meningitidis is the most common cause of meningitis in persons between the ages of [blank_start]2 and 18[blank_end] years adding up to around [blank_start]2,000[blank_end] cases annually (this is an underestimate as only half are confirmed in the laboratory. It possesses a [blank_start]polysaccharide[blank_end] capsule, which is the main antigen and determines the [blank_start]serotype[blank_end] of the species. There is at least [blank_start]13[blank_end] different serotypes the most commonly implicated include A, B, C and [blank_start]W135[blank_end]. The serotype prevalence changes with time and [blank_start]geographical[blank_end] location.

Pathogenicity involves [blank_start]Pili-mediated[blank_end], receptor-specific [blank_start]colonization[blank_end] of [blank_start]nonciliated[blank_end] cells of nasopharynx (this allows [blank_start]adherence[blank_end] to host epithelium). Antiphagocytic polysaccharide capsule allows [blank_start]systemic spread[blank_end] in absence of specific immunity. Toxic effects mediated by [blank_start]hyperproduction[blank_end] of lipooligosaccharide ([blank_start]endotoxin[blank_end]) [blank_start]IgA[blank_end] protease. It cleaves the IgA [blank_start]antibodies[blank_end] present in [blank_start]respiratory[blank_end] mucosa. Facilitates the release of its functional passenger domain from its cell-bound [blank_start]carboxy-terminal[blank_end] transporter domain. IgA protease is present only in [blank_start]pathogenic[blank_end] Neisseria species. IgA protease can also cleave a similar site in the [blank_start]host lysosomal[blank_end] LAMP1 (lysosome-associated membrane protein 1). Although cleavage of IgA1 prolongs bacterial extracellular survival at mucosal locations, cleavage of LAMP1 may be important for the [blank_start]intracellular survival[blank_end] of the pathogens The antigen binding to macrophages causes release of TNF which is typical in cytokine storms of toxic shock, it also increases membrane permeability allowing CSF infection. Serogroups A, B, C, Y, W135 account for about [blank_start]90[blank_end]%, the incidence of particular serotypes has reduced due to implication of targeted vaccinations. The latest vaccine [blank_start]Menactra[blank_end] was licensed in [blank_start]2005[blank_end] and is protective against all common serotypes apart from [blank_start]B[blank_end].

Phases of [blank_start]antigen variation[blank_end] include Mutational changes to surface facing, often immunogenic, cellular components. Variation of one or more enzymes involved in [blank_start]LPS biosynthesis[blank_end] or of distinct [blank_start]Opa[blank_end] proteins. The main subunit of PilE (pilin), that makes up the pilus fibre, develops variations arising from [blank_start]intergenomi[blank_end]c and [blank_start]intragenomic[blank_end] recombinase A-dependent [blank_start]recombination events[blank_end] between one of several pilS (silent) pilin genes and pilE, the expressed pilin gene. Recently discovered molecules include [blank_start]RTX-[blank_end]like molecules these are [blank_start]iron-regulated[blank_end] proteins termed [blank_start]FrpA[blank_end] and [blank_start]FrpC[blank_end]. Homologous to the RTX (repeat-in-toxin) family of proteins of many Gram-negative bacteria that function as cytolysins or proteases do not seem to be essential for disease but are expressed during disease and may have a role in bacterial [blank_start]dissemination[blank_end].