Neisseria Meningitidis Flashcards
What are some important virulence factors for N. meningitidis?
Polysaccharide capsule
Capsule switching
Type IV pili
Micro-colony formation/adhesion in the nasopharynx
Lipo-oligosaccharide (LOS)
Which serotypes of N. meningitidis cause invasive disease?
A, B, C, Y, W-135, X
Which serotypes of N. meningitidis are for carriage?
29E, H, I, K, L, Z
What is capsule switching in N. meningitidis?
The change of meningococcal capsule structure
Transformation and homologous recombination of the capsule locus was first seen in serogroup B
What do type IV pili do?
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
How does the LOS cause virulence in N. meningitidis?
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
What does N. meningitidis require for survival?
Iron is required for survival, colonization, and infection
How does N. meningitidis obtain iron?
It scavenges iron from the human proteins transferrin, lactoferrin, and hemoglobin through a series of evolved surface-exposed receptors
What is the purpose of PorB in N. meningitidis?
It is the major outer membrane porin which induces calcium ion flux and activates Toll-like receptor 2 and apoptosis
What are the proteins Opa and Opc involved in for N. meningitidis?
Important in adherence
What is factor H binding protein and Neisseria heparin binding antigen?
Lipoproteins involved in meningococcal resistance to complement-mediated killing
How does N. meningitidis interact with the nasopharyngeal mucosa?
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
How does N. meningitidis invade the meninges?
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
Which medium is used to culture N. meningitidis?
Chocolate agar
How does N. meningitidis respond to an oxidase test?
It is oxidase positive as it contains cytochrome C and can therefore use oxygen for energy production (ETC)
Which sugars does N. meningitidis ferment?
It ferments glucose and maltose while N. gonorrheoeae only ferments glucose
What does RT PCR test in N. meningitidis?
Targes the ctrA gene of the bacteria which is a capsular polysaccharide transport protein and tests for serogroups A, B, C, Y, W-135
What are the risk factors for disease caused by N. meningitidis?
Serogroup (A, B, C, X, Y, W-135)
Nasopharyngeal carriage
Waning immunity
Environmental factors
Demographic factors
Socioeconomic factors
Concurrent infections
Which populations have a higher change of invasive disease due to N. meningitidis?
Higher in children
Higher in people with terminal complement deficiency or post-splenectomy
What is the incubation period of N. meningitidis?
1-10 days
Usually less than 14 days
How is N. meningitidis transmitted?
Person-to-person contact with respiratory droplets of infected people = droplet transmission
What is the meningitis belt?
Outbreaks every 8-12 years in the past 50 years
Describe conjugate vaccines used for N. meningitidis
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
Why is serogroup B not part of any N. meningitidis vaccines?
Because we are worried about triggering an autoimmune response and vaccines that use those proteins aren’t that effective
Which antibiotics are used to treat N. meningitidis?
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
What is used for prophylaxis of contacts in the case of exposure to N. meningitidis?
Rifampin which inhibits bacterial DNA-dependent RNA polymerase
