Neisseria Meningitidis

Question 1

What are some important virulence factors for N. meningitidis?

Answer 1

Polysaccharide capsule
Capsule switching
Type IV pili
Micro-colony formation/adhesion in the nasopharynx
Lipo-oligosaccharide (LOS)

Question 2

Which serotypes of N. meningitidis cause invasive disease?

Answer 2

A, B, C, Y, W-135, X

Question 3

Which serotypes of N. meningitidis are for carriage?

Answer 3

29E, H, I, K, L, Z

Question 4

What is capsule switching in N. meningitidis?

Answer 4

The change of meningococcal capsule structure
Transformation and homologous recombination of the capsule locus was first seen in serogroup B

Question 5

What do type IV pili do?

Answer 5

Pili facilitate initial attachment and anchoring to human epithelial or endothelial cells

Pilus attachment to human cells initiates localized reorganization of the host cell cytoskeleton and also facilitates aggregation and microcolony formation

Activates signaling pathways in endothelial cells

Contribute to cortical plaque formation which facilitates adhesion and meningococcal entry into cells

Question 6

How does the LOS cause virulence in N. meningitidis?

Answer 6

It has a lipid A structure distinct from Gram-negative enterics but able to cause systemic inflammation in the same manner

More potent then LPS of enteric Gram-negative bacilli

Influences meningococcal attachment and invasion of host cells and complement-mediated killing

Question 7

What does N. meningitidis require for survival?

Answer 7

Iron is required for survival, colonization, and infection

Question 8

How does N. meningitidis obtain iron?

Answer 8

It scavenges iron from the human proteins transferrin, lactoferrin, and hemoglobin through a series of evolved surface-exposed receptors

Question 9

What is the purpose of PorB in N. meningitidis?

Answer 9

It is the major outer membrane porin which induces calcium ion flux and activates Toll-like receptor 2 and apoptosis

Question 10

What are the proteins Opa and Opc involved in for N. meningitidis?

Answer 10

Important in adherence

Question 11

What is factor H binding protein and Neisseria heparin binding antigen?

Answer 11

Lipoproteins involved in meningococcal resistance to complement-mediated killing

Question 12

How does N. meningitidis interact with the nasopharyngeal mucosa?

Answer 12

Meningococci attach to nonciliated nasopharyngeal epithelial cells and induce apical cortical plaques, which anchor the organism against loss by mucus and ciliary action

This promotes the formation of meningococcal microcolonies and biofilms

The induction of cortical plaques also leads to the internalization of meningococci within epithelial cells which is a gateway to the bloodstream and meninges

Question 13

How does N. meningitidis invade the meninges?

Answer 13

There is a breakdown of the tight junctions between endothelial cells which can allow meningococci to cross the BBB and gain access to the subarachnoid space

Question 14

Which medium is used to culture N. meningitidis?

Answer 14

Chocolate agar

Question 15

How does N. meningitidis respond to an oxidase test?

Answer 15

It is oxidase positive as it contains cytochrome C and can therefore use oxygen for energy production (ETC)

Question 16

Which sugars does N. meningitidis ferment?

Answer 16

It ferments glucose and maltose while N. gonorrheoeae only ferments glucose

Question 17

What does RT PCR test in N. meningitidis?

Answer 17

Targes the ctrA gene of the bacteria which is a capsular polysaccharide transport protein and tests for serogroups A, B, C, Y, W-135

Question 18

What are the risk factors for disease caused by N. meningitidis?

Answer 18

Serogroup (A, B, C, X, Y, W-135)
Nasopharyngeal carriage
Waning immunity
Environmental factors
Demographic factors
Socioeconomic factors
Concurrent infections

Question 19

Which populations have a higher change of invasive disease due to N. meningitidis?

Answer 19

Higher in children
Higher in people with terminal complement deficiency or post-splenectomy

Question 20

What is the incubation period of N. meningitidis?

Answer 20

1-10 days
Usually less than 14 days

Question 21

How is N. meningitidis transmitted?

Answer 21

Person-to-person contact with respiratory droplets of infected people = droplet transmission

Question 22

What is the meningitis belt?

Answer 22

Outbreaks every 8-12 years in the past 50 years

Question 23

Describe conjugate vaccines used for N. meningitidis

Answer 23

The CRM-197 carrier protein is used for conjugation and is for serogroup C only

Similar to WT diphtheria toxin except for an amino acid change (glycine to glutamic acid at position 52 in the 535 amino acid chain)

Easy to produce in large amounts

Conjugation leads to T-cell-dependent antigen-recruitment of T-cell help by the carrier protein

Question 24

Why is serogroup B not part of any N. meningitidis vaccines?

Answer 24

Because we are worried about triggering an autoimmune response and vaccines that use those proteins aren’t that effective

Question 25

Which antibiotics are used to treat N. meningitidis?

Answer 25

Cell wall inhibitors = third-generation cephalosporins (ceftriaxone is good at crossing the BBB)

Binds to one or more of the penicillin-binding proteins which inhibits the final transpeptidation step of peptidoglycan in the bacterial cell wall

Question 26

What is used for prophylaxis of contacts in the case of exposure to N. meningitidis?

Answer 26

Rifampin which inhibits bacterial DNA-dependent RNA polymerase