Neisseria Flashcards
Show a Phylogenetic Overview of Bacteria
This is based on 16S rRNA sequencing
Show a Phylogenetic Tree of the Proteobacteria
Neisseriales: state the order, familiy, genus and species
What are the physical characterisitics of Neisseria?
- Diplococcus
Flat sides with division plane
- 6-1 µm
* Fastidious growth requirement
May include
AA, Purines/pyrimidines, Vitamins
- 35-37°C, humid
- Aerobic / Capnophilic
Like raised CO2 5%
What are the chemical characteristics of neisseria?
- Oxidase positive
- Catalase-positive
H2O2 >>> O2 & H2O
Reaction to 3% H2O2
Gonococcus – strong positive
Meningococcus – variable positive
- Acid from sugars (oxidative)
Useful for differentiating Neisseria sp.
Neisseria – Describe its Gram negative envelope
Non-motile
Gram-negative:
- Two membranes
- LPS
- Thin PG layer
- OMPs
Neisseria - Pili
- Important for pathogenesis
- Mediate attachment
- Tip = adhesin (Pil C)
- Binds CD46
Neisseria - Describe its Pili
- Repeating sub-units of pilin (pil E) - expressed
- N terminus constant (from 5’ of gene)
- C terminus highly variable (from 3’ of gene)
- Many 5’ truncated genes for C terminus of pilin (Pil S) – silent
- Recombination generates diversity
- Antigenic Variation
–Many antigenically distinct pili (106+)
•Phase variation
–Rapid alteration in expression
Neisseria – Describe its Endotoxin (LOS)
•LipoOLIGOsaccharide
•Lacks O Ag
–Small but deadly
•Antigenic variation
–Core sugars
•Low Sialic Acid
–Efficiently infect mucosae
–Easily killed
•High Sialic Acid
–Less infective BUT
–Protected from serum
Neisseria – Descrivbe Endotoxin (LOS) release
- Can be released in blebs during division
- Outer membrane blebs
- ‘Microparticles’
- Accounts for most of the features of Neisseria disease
- Decoys
OMPs: Porin proteins (por A and por B)
–Inhibit phagosome maturation
–Porin can translocate into host membrane
–Increases intracellular survival
OMPs: Reduction modifiable proteins
–Size is changeable on Western blot via redox
–Protect Ags from Abs
–ONLY found in pathogenic Neisseria
–Immunogenic – Abs are variably protective
What is the functin of Opa?
- Mediate tight-binding to cells
- 3+ Opa proteins
- Phase variation – a range of permutations
- Two hypervariable domains (extracellular)
–Point mutations -> new Opa variants
N. meningitidis – Describe the 2 groups based on Opa receptors
Opa HS - heparan sulphate & ECM (Fn/Vn)
- Direct via HS; indirect to integrins via Fn/Vn ‘bridge’
- Integrins INTEGRATE extracellular & intracellular environment
- Signals for cytoskeletal rearrangement for UPTAKE
–Opa CEA – binds CEA-cell adhesion molecules
Describe the Neisseria capsule
- Extracellular, polysaccharide
- Major virulence factor of meningococcus
–Acapsular strains rarely cause disease
- Basis of serogroups
- 13 capsule types – 5 cause 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
Describe Iron Acquisition
- Iron limitation is a problem for bacteria
- Neisseria are very capable iron ‘grabbers’:
–Transferrin-binding protein
–Lactoferrin-binding proteins
–Haemoglobin-binding proteins
Draw a table comparing Meningococcus and Gonococcus
Describe Infection process
Adhesion to epithelial cells
- Respiratory epithelium
- Pili – initial binding
- Opa – tight binding
Division
Infection process: Endocytosis
Pili and Opa can stimulate cytoskeletal rearrangements
Membrane protrusions formed
LOS has an essential role in this
Infection process
Infection process: Endocytosis – pathogen-stimulated
•Transcytosis
Infection process- transcytosis
Once inside……capsule is important for survival
Host Defence: Describe how the innate and adaptive immuity contribute
•Innate Immunity
–Mucociliary escalator
–Anti-microbial effectors
•Defensins, lysozyme, lactoferrin
•Adaptive Immunity
–sIgA
- Aim is for Ab to neutralise infectivity (blocking adhesins)
- Some will be targeted by the meningococcus IgA protease (cleaves IgA1). IgA2 remains.
Describe the Host-defence - once inside
•Complement
- Classical pathway
- Alternative pathway
- Lectin pathway
•Maternal IgG protects to 6 months
–6+ months babies are highly susceptible
How is Complement important in Neisseria defence?
Describe Neisseria & complement evasion
•Recruit factor H (& I)
–Via Porin
–Via Sialic acid
–Reduced C3 convertase
•Recruit C4bp (& I)
–Via pilin
–Reduced C3 convertase
•Survival in sub-mucosae
