Biology of Neisseria Meningitides Flashcards
What type of bacteria is N.meningitides?
gram negative diplococcus
Where does N.meningitides reside?
obligate human parasite- extracellular
How is N.meningitides classified?
into serogroups based on capsular polysaccharide- A,B,C, W135, Y and X
Where in the body does meningococcus colonise?
nasopharynx
How is meningococcus transmitted?
coughing; sneezing; kissing etc
What are the features of meningococcus that makes it so pathogenic?
able to adhere to and cross host barriers; evasion; induces strong inflammatory repsonse
Which cellular barriers is meningococcus able to adhere to and cross?
epitheium of respiratory tract; endothelium and BBB
What is the name for the leakage that replication and damage by meningococcus in blood vessels causes?
meningococcal leakage
Where are the virulence attributes of microbes found?
on the cell surface
What is the most important factor in allowing meningococcus to adhere to and cross barriers?
type IV pili
things does Tfp allow meningococcus to do?
adhesion to host cells; aggregation; twitching motility; natural transformation
What is natural transformation?
gaining of genes from the environment
What does aggregation mediated by Tfp allow meningococcus to do?
form biofilms in blood vessels
Describe twitching motility?
extends and contracts- attaches then pulls itself towards
What protein is Tfp a polymer of?
pillins
Describe Tfp?
thin; long and flexible filaments- which look like a lollipop-globular head with hydrophobic residues forming the stick
What imaging can be used to look at the filaments?
cryoelectronic microscopy
What suggests that pilli is conserved?
all bacteria with pilli have the same proteins used to attach it to membrane
Name other type IV filamentous nanomachines?
secreton; competence psudeopilus; archaellum
Which cells have type IV filamentous nano-machines?
ubiquitous in prokaryotes
How are type IV pillins made?
pillins are synthesised as propeptide and stay in inner membrane; then leader sequence is cleaved and ATP is used to push pillins out of IM where pillin polymerises; uses a pore (secreton) to move through OM
What are the 2 types of opacity proteins?
Opa proteins and Opc
What is the function of opacity proteins?
role in adhesion- but nowhere near as important as type IV pilli
Why are the opacity proteins named so?
presence confers opacity on bacteria in stereomicroscopy
What is hte strucutre of opacity proteins?
have beta-barrel with exposed surface loops which are responsible for adhesion
What is result of binding to OpaHS?
internalisation
What is hte result of binding to OpaCEA?
uptake and transcytosis
When is opa-mediated adhesion particularly important?
in the absene of the capsule (usually covered)
What is the capsule?
water soluble high molecular weight polysaccharide made of regularly mediated subunits of sugars
What is different about hte different serogroup polysaccharide?
different sugars or same sugar with different branching pattern
What is the capsule especially important in protection against?
complement-mediated lysis: as complement isn’t able to access OM
Which strains of meningococcus have a capsule?
all invasive strains (needed for invasion) but only 50% of carriage isolates
What are the functions of the 3 regions of the capsule locus?
A-synthesis and polymerisation (different across the serogroups); B-anchoring in membrane through addition of a lipid; C-translocation across OM and IM
What is FHbp?
factor H binding protein: surface lipoprotein
What is the structure of FHbp?
folded into 2 beta-barrels
What are the 2 forms of neisseria which are pathogenic?
gonoccocus and meningitides
How did neisseria acquire a capsule?
through horizontal gene transfer
Why is gonoccocus not invasive?
does not have capulse locus
What is factor H?
a large, soluble glycoprotein which regulates complement by protecting host cells and tissues from famage by complement activation
What does factor H bind?
host sugars and C3b- accelerating its decay
What is FHbp an example of?
bacterial mimicry: binds factor H using same stereochemistry as host sugars
What is antigenic variation?
non-reversible important changes in DNA sequence which alter protein sequence
What is phase variation?
reversible small changes in DNA sequence which alter gene expression
Through what mechanism does phase variation occur?
slipped-strand mispairing
What induces slipped-strand mispairing?
repetitive sequences within genes or their promoters
What are the 2 methods of modification of surface structures?
antigenic and phase variation
Why is modification of surface structures important?
key in allowing bacterium to disguise itself
How does pilin antigenic variation arise?
gene conversion: a silent gene can replace part of hte pilus gene (the part which ends up exposed on surface of Tfp) through homologous recombination
Which genes in meningococcus undergo phase variation?
those associated with virulence
What are porins?
integral OM proteins with multiple surface loops which are highly immunogenic (elicit antibodies)
How does slip-strand mismatching work?
when DNA polymerase comes across certin sequences of repeated basses, stutters and makes a mistake changing the expression of the gene
What is HGT?
transfer of genes between isolates in a manner other than traditional reproduction
What is the main method of HGT?
natural tranformation (acquisition of free DNA)
What mediates DNA uptake by meningococcus?
Tfp- binds and on retraction beings DNA across OM then another protein facilitates movement across IM
What is LPS composed of?
lipid A and sugar chain which some immunotypes modified with a sialic acid addition
How do meningococci release massive amounts of LPS into the bloodstream?
by releasing blebls of the outer membrane (not all gram negs do this which is why not all cause cytokine storm)
What can the level of LPS in the patients bloodstream be correlated with?
infection outcome
