Bacterial capsules Flashcards
whats the Structure of bacterial capsules?
• network of acidic polysaccharide
- anchored to OM by covalently to phospholipids or lipid A
• Each capsule contains one type of polysaccharide- oligosaccharide units joined by glycosidic linkages
• Polysaccharide chains are diverse, differing in constituent sugars, branching, linkages, group substitutions
• Antigenic diversity
how diverse are Ag?
– P. aeruginosa, 80 serotypes
– E. coli, ~80 serotypes
– S. pneumoniae, ~90 serotypes
what the diversity of the E. coli capsule?
- K antigens ~80 different serotypes
- Four capsular types with two distinct assembly systems (groups 1 and 4 vs 2 and 3)
- Assembly systems for groups 2 and 3 are encoded by single chromosomal locus
whats the genetic structure of the e.coli capsule?
- Regions 1 assembly & translocation 6-8kb
- region 2 is serotype specific synthesis/polymerisation 6kb
- region 3 export 3 kb
- 1+3 conserved
what are the components of Capsules of E. coli assembly
KfiABCD - polymerisation KpsCMST – translocation & export KpsU – polymer growth KpsD – OM transport KpsE – membrane fusion
give an Overview of functions of bacterial capsules
- Prevent Desiccation
- Serum resistance
- ADHERENCE (+/-)
- IMMUNE EVASION
- Weak immunogens
- Molecular mimicry
- Antigenic/Phase Variation
what are the Functions of bacterial capsules?
- regulate access of molecules and ions
- retain nutrients for bacterial growth
- prevent desiccation during transmission from host to host
- promote adherence to surfaces and other bacteria
- inhibit adherence e.g. in Streptococcus pneumoniae; proposed that amounts of capsular material vary at different stages of pathogenesis
when is the capsule required?
- not required for normal growth in vitro
- required for survival in host body
- isolates from invasive infection are encapsulated, but lose capsule when sub-cultured in laboratory conditions
how does the capsule preform its Major role in evasion of the host immune system
- weakly immunogenic, poor activators of complement
- inhibit opsonisation
- negative charge repels phagocytes (sialic acid)
- shedding removes bound antibodies and complement components
describe the Capsules of E. coli’s antigen diversity
• Different components:
– K1: sialic acid
– K20: ribose+KDO
• Different structures:
– some straight chain molecules, others branched
– side group substitutions
• K18 and K22 both ribose + ribitol phosphate
• only difference - in K18 ribose is O-acetylated
• difference due to altered expression of a trans-
acetylase – enzyme inactive or repressed in K22
• serotypes unstable
– pure population can revert to K18/K22 mix
what is Molecular mimicry?
• E. coli K1 - a-2,8 linked sialic acid identical to capsules of:
– Neisseria meningitides group B (meningitis in adults)
– Pasteurella haemolytica (pasteurellosis in lambs)
• silica acid residues with a a-2,8 linkage found on surfaces of eukaryotic cells - glycoconjugates on the neural cell
adhesion molecule (NCAM)
• immunologically recognised as “self” molecular mimicry
why are K antigens less virulent?
slightly different sialic acid not recognised as self - more immunogenic, less virulent:
– K1+ : SA is O-acetylated
– N. meningitidis group C: SA is a-2,9 linked
– K92: SA is a-2,9 and a-2,8 linked
give 3 examples of molecular mimicry
- E. coli K5: glucuronic acid and N-acetylglucosamine
mimics an intermediate in heparin biosynthesis - E. coli K4: identical with chondroitin, a constituent
of extracellular matrix - Streptococcus pyogenes capsule: hyaluronic acid
what is Capsules of E. coli’s role in disease
- small fraction of ~80 K antigens associated with disease
- >90% of E. coli from neonatal meningitis are K1
describe neonatal meningitis
– affects 1 in 2-4000 infants
– initial infection of blood invasion from GI tract or
nasopharynx but tropism for meninges (in brain)
– pathology inflammation of meninges
– sudden onset, kill within 24h, 40% mortality rate
– survivors may have irreversible neurological damage
