Biology of Neisseria Meningitides

Question 1

What type of bacteria is N.meningitides?

Answer 1

gram negative diplococcus

Question 2

Where does N.meningitides reside?

Answer 2

obligate human parasite- extracellular

Question 3

How is N.meningitides classified?

Answer 3

into serogroups based on capsular polysaccharide- A,B,C, W135, Y and X

Question 4

Where in the body does meningococcus colonise?

Answer 4

nasopharynx

Question 5

How is meningococcus transmitted?

Answer 5

coughing; sneezing; kissing etc

Question 6

What are the features of meningococcus that makes it so pathogenic?

Answer 6

able to adhere to and cross host barriers; evasion; induces strong inflammatory repsonse

Question 7

Which cellular barriers is meningococcus able to adhere to and cross?

Answer 7

epitheium of respiratory tract; endothelium and BBB

Question 8

What is the name for the leakage that replication and damage by meningococcus in blood vessels causes?

Answer 8

meningococcal leakage

Question 9

Where are the virulence attributes of microbes found?

Answer 9

on the cell surface

Question 10

What is the most important factor in allowing meningococcus to adhere to and cross barriers?

Answer 10

type IV pili

Question 11

things does Tfp allow meningococcus to do?

Answer 11

adhesion to host cells; aggregation; twitching motility; natural transformation

Question 12

What is natural transformation?

Answer 12

gaining of genes from the environment

Question 13

What does aggregation mediated by Tfp allow meningococcus to do?

Answer 13

form biofilms in blood vessels

Question 14

Describe twitching motility?

Answer 14

extends and contracts- attaches then pulls itself towards

Question 15

What protein is Tfp a polymer of?

Answer 15

pillins

Question 16

Describe Tfp?

Answer 16

thin; long and flexible filaments- which look like a lollipop-globular head with hydrophobic residues forming the stick

Question 17

What imaging can be used to look at the filaments?

Answer 17

cryoelectronic microscopy

Question 18

What suggests that pilli is conserved?

Answer 18

all bacteria with pilli have the same proteins used to attach it to membrane

Question 19

Name other type IV filamentous nanomachines?

Answer 19

secreton; competence psudeopilus; archaellum

Question 20

Which cells have type IV filamentous nano-machines?

Answer 20

ubiquitous in prokaryotes

Question 21

How are type IV pillins made?

Answer 21

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

Question 22

What are the 2 types of opacity proteins?

Answer 22

Opa proteins and Opc

Question 23

What is the function of opacity proteins?

Answer 23

role in adhesion- but nowhere near as important as type IV pilli

Question 24

Why are the opacity proteins named so?

Answer 24

presence confers opacity on bacteria in stereomicroscopy

Question 25

What is hte strucutre of opacity proteins?

Answer 25

have beta-barrel with exposed surface loops which are responsible for adhesion

Question 26

What is result of binding to OpaHS?

Answer 26

internalisation

Question 27

What is hte result of binding to OpaCEA?

Answer 27

uptake and transcytosis

Question 28

When is opa-mediated adhesion particularly important?

Answer 28

in the absene of the capsule (usually covered)

Question 29

What is the capsule?

Answer 29

water soluble high molecular weight polysaccharide made of regularly mediated subunits of sugars

Question 30

What is different about hte different serogroup polysaccharide?

Answer 30

different sugars or same sugar with different branching pattern

Question 31

What is the capsule especially important in protection against?

Answer 31

complement-mediated lysis: as complement isn't able to access OM

Question 32

Which strains of meningococcus have a capsule?

Answer 32

all invasive strains (needed for invasion) but only 50% of carriage isolates

Question 33

What are the functions of the 3 regions of the capsule locus?

Answer 33

A-synthesis and polymerisation (different across the serogroups); B-anchoring in membrane through addition of a lipid; C-translocation across OM and IM

Question 34

What is FHbp?

Answer 34

factor H binding protein: surface lipoprotein

Question 35

What is the structure of FHbp?

Answer 35

folded into 2 beta-barrels

Question 36

What are the 2 forms of neisseria which are pathogenic?

Answer 36

gonoccocus and meningitides

Question 37

How did neisseria acquire a capsule?

Answer 37

through horizontal gene transfer

Question 38

Why is gonoccocus not invasive?

Answer 38

does not have capulse locus

Question 39

What is factor H?

Answer 39

a large, soluble glycoprotein which regulates complement by protecting host cells and tissues from famage by complement activation

Question 40

What does factor H bind?

Answer 40

host sugars and C3b- accelerating its decay

Question 41

What is FHbp an example of?

Answer 41

bacterial mimicry: binds factor H using same stereochemistry as host sugars

Question 42

What is antigenic variation?

Answer 42

non-reversible important changes in DNA sequence which alter protein sequence

Question 43

What is phase variation?

Answer 43

reversible small changes in DNA sequence which alter gene expression

Question 44

Through what mechanism does phase variation occur?

Answer 44

slipped-strand mispairing

Question 45

What induces slipped-strand mispairing?

Answer 45

repetitive sequences within genes or their promoters

Question 46

What are the 2 methods of modification of surface structures?

Answer 46

antigenic and phase variation

Question 47

Why is modification of surface structures important?

Answer 47

key in allowing bacterium to disguise itself

Question 48

How does pilin antigenic variation arise?

Answer 48

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

Question 49

Which genes in meningococcus undergo phase variation?

Answer 49

those associated with virulence

Question 50

What are porins?

Answer 50

integral OM proteins with multiple surface loops which are highly immunogenic (elicit antibodies)

Question 51

How does slip-strand mismatching work?

Answer 51

when DNA polymerase comes across certin sequences of repeated basses, stutters and makes a mistake changing the expression of the gene

Question 52

What is HGT?

Answer 52

transfer of genes between isolates in a manner other than traditional reproduction

Question 53

What is the main method of HGT?

Answer 53

natural tranformation (acquisition of free DNA)

Question 54

What mediates DNA uptake by meningococcus?

Answer 54

Tfp- binds and on retraction beings DNA across OM then another protein facilitates movement across IM

Question 55

What is LPS composed of?

Answer 55

lipid A and sugar chain which some immunotypes modified with a sialic acid addition

Question 56

How do meningococci release massive amounts of LPS into the bloodstream?

Answer 56

by releasing blebls of the outer membrane (not all gram negs do this which is why not all cause cytokine storm)

Question 57

What can the level of LPS in the patients bloodstream be correlated with?

Answer 57

infection outcome