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
why is K1 a successful virulence factor?
- K1 sialic acid
- Required for evasion of host defence, and tropism and invasion of brain endothelium
- successful as very weak immunogen
Capsules of meningococci and H. influenzae role in disease
- High frequency of asymptomatic carriage in upper respiratory tract
- Meningococci frequently cause septicemia by high levels of bacteria in the blood
- Invasion of meninges leads to meningitis
- Incidence of bacterial meningitis in the UK is ~1/100,000 people
- Death occurs in 5-10% of people with serious sequelae in 20% of survivors
name the Disease-causing serogroups of H. influenzae
b (H. influenzae, Hib)
• Insertion of capsule of Hib into an acapsulate mutant of strain Rd restored bacteremia in animals
how do Capsular Vaccines work?
Capsular polysaccharide is conjugated to protein (diptheria toxin) to stimulate a T-cell dependent immune response
explain the flu vaccine
Haemophilus influenzae serogroup b vaccine introduced into UK in 1992 resulting in major drop in cases of meningitis due to this bacteria
what is the MenC vaccine?
Neisseria meningitidis serogroup C vaccine introduced in 1999 almost eradicated disease due to this serogroup
name 5 Modes of transmission
– Fecal-oral route – Oral route – droplets/sputum - direct – Fomite (infectious environmental surfaces) – Sexually transmitted – Vector borne
what are the Requirements/Implications of Transmission
- Frequent release of large numbers of organisms
- Environmental survival – Desiccation – Spores
- Bottlenecks– Small populations impose restrictions on genetic variation
how does Virulence Correlate with Transmission
- Model using Citrobacter rodentium in mice mimics enterpathogenic E. coli infections of humans
- Type III secretion system is required for virulence so investigated mutants of this system
- Mice are coprophagic resulting in efficient fecal- oral transmission
- Infected mice are co-housed with uninfected mouse and examined for signs of morbidity/mortality
Bacterial capsules - Summary
- Capsules are polymers of acidic subunits attached to outer membrane
- Multiple genes present in single genetic locus are responsible for biosynthesis, assembly and export of capsules
- Capsules have multiple functions with effects on adherence, immune evasion and transmission
- Capsule are a major determinants of virulence in E. coli and for meningitis
- Transmission requires resistance to desiccation for fecal and oral pathogens
- Virulence enhances transmission
