GRAM-NEGATIVE COCCI: NEISSERIA Family = Neisseriaceae, Genus = Neisseria, Species = gonorrheae / meningitidis Eikenella and Kingella are also within the same family however they are rarer and opportunistic (usually only infected if been bitten by someone else) CHARACTERISTICS . Non-motile · Gram-negative · Diplococcus = flat sides, 0.6-1um · Fastidious growth requirement = needs specialist things to survive (e.g. aa, purines/ pyrimidines, vitamins) · 35-37°?, humid · Aerobic / capnophillic (high carbon dioxide) · Oxidase positive · Catalase positive · Gonococcus = strong positive · Meningococcus = variable positive · Metabolism of sugars used to differentiate the Neisseria species · Gonococcus = only glucose positive · Meningococcus = glucose and maltose positive · Meningococcus is commensal, unlike gonococcus · Both target epithelium · Gonococcus = genital tract · Meningococcus = nasopharynx · Meningococcus is more invasive than gonococcus · Both cause a purulent infection (large neutrophil involvement) CELL WALL STRUCTURE Pilli · Tip = adhesin (Pil C) binds CD46 to mediate attachment - important for pathogenesis · Repeating subunits of pillin (pil E - expressed) · N terminus (from 5' of gene) = constant · C terminus (from 3' of gene) = highly variable · Many 5' truncated genes for C terminus of pillin (Pil S - silent) · Recombination generates the diversity to avoid the immune system · Antigenic variation = many antegenically distinct pilli (10,000,000 +) · Phase variation = rapid alteration in expression Endotoxin (LOS) · Lipooligosaccharide - contains lipid A, inner and outer core (lacks O-antigen) · Small but deadly · Antigenic variation of core sugars to avoid immune system · Sialic acid · Low = efficiently infect mucocae, easily killed · High = less infective, protected from serum · Can be released as blebs during division · Microparticles · Accounts for most of the Neisseria disease · Decoys for immune system Major Outer Membrane Proteins (MOMPs) · I, II, III = Porin · Inhibit phagosome maturation . Porin can translocate into host membrane
· Increases intracellular survival · IV = RMP-Reduction modifiable proteins · Size is changeable on Western blot via redox · Protect antigens from antibodies - immunogenic · Only found in pathogenic Neisseria · V = Opa Opacity · Mediate tight-binding to cells - allows a focus of infection · Two hypervariable domains (point mutations) · Opa HS = heparan sulphate (dripping with sugars) · Direct via HS / indirect to integrins via Fn/Vn 'bridge' · Integrins integrate extracellular and intracellular environment · Stimulates the host cell to uptake the pathogen via cytoskeletal rearrangement · Opa CEA · Binds CEA-cell adhesion molecules Capsule · Extracellular polysaccharide · Major virulence factor of meningococcus - acapsular strains rarely cause disease · Basis of serogroups - 13 capsule types with 5 causing disease (A, B, C, Y, W135) · Serogroup A = N-acetylmannosamine-1-phosphate · Serogroup B, C, Y, W135 = sialic acid-based · Major component of vaccines · Capsular variation can occur - horizontal DNA transfer Iron Acquisition · Iron limitation is a problem -