Lecture 16 Neisseria Flashcards
What are the different species of Neisseria?
pathogens:
- N gonorrhoeae
- N meningitidis
Commensals:
Many (eg N lactamica)
Neisseria are structurally identified by..?
- gram negative diplococci
- non-motile, non- sporeforming
How is Neisseria grown in cx?
-requires enriched CO2 in medium
-oxidase-positive
-Pathogens utilize different sugars:
Gnonococcus: glucose
Meningococcus: maltose and glucose
What is the host range?
- obligate human pathogens
- no good animal model to study
What are structures found in both pathogens?
- G- cell wall
- Major antigens are pili, outer membrane proteins (Por, Opa), LOS (lipooligosaccharide)
What are two host receptors that are utilized by pili?
- CD46 on male urogenital epithelial cells
- CR3 on female cervical epithelium
How is the expression of pili controlled?
Phase variation (transcriptional)
What is the antigenic variation in Pili?
- conserved regions and 6 immunodominant variable regions
- on antigenic type at a time, multiple present but are silent
- expression occurs at one active site
What causes antigenic variation in pili?
-recombination (non-reciprocal) via intrachromosomal or via transformation.
What are two outer membrane protein?
- Por
- Opa
What is Por?
(OMP I)
- Por most abundant structural protein
- Trimers: porin function
- involved in attachment and invasion of host cells by binding to host CR3 receptor
Why is serotyping scheme based on Por?
-each strain has one antigenic type, but there is variation
among strains
Por 1A - (disseminated infection)
Por 1B - (local genital infection)
What is Opa?
(Omp II)
- compromises group of 12 genes (3-4 in meningiditis)
- 0-3 Opa proteins may be expressed in single strain
- expression determines colony phenotype: opaque or transparent
- functions in close attachment to host cells
- Phase switch depending on environment
How is Opa genetically controlled?
- Multiple gene copies, all with promoters
- constitutively transcribed
- translationally controlled
- CTCTT repeats immediately proceeds genes, puts it in or out of phase
What is LOS?
Similar to LPS, but lacks repeating sugar subunit.
- major role in production of inflammatory mediators
- plays a role in attachment
What is Sialylated LOS?
confers serum resistance and attenuates the inflammatory response
What is the pathogenesis in Male vs Female GC?
- infection of males leads to acute urethritis
- infection in females is asymptomatic
What is the mechanism of male pathogenesis of GC?
- attachment to CD46 receptor in urethral epithelium
- Opa expression results in closer adhesion in gonococci and host cells
- GC multiply, reach submucosa, triggers inflammation, can have hematogenous extension.
What is the mechanism of pathogenesis of GC in females?
-Pili and por bind to CR3 in epithelial cells, does not trigger inflammatory response
What is the host immune response to Neiserria G?
- Natural abx develop from colonization with commensal Neisseria and other gram-negative organism
- results in ability of NHS + C to kill many strains
- Bactericidal abx (IgM, IgA, IgG).
- opsonic abx
- ingested, but not killed by neutrophils
What is the epidemiology and transmission of GC?
- Mostly through sexual transmission, male to female.
- higher rates in non-whites
- asymptomatic (more in females) make it hard to eradicate
What is the clinical spectrum manifestations of GC?
- Urethritis
- Cervicitis
- Salpingitis
- Disseminated Infection • Conjunctivitis (infants)
- Rectal
What are the sx of Urethritis?
- Incubation period: 1-14 days; majority develop symptoms in 2-5 days
- Symptoms: dysuria and/or urethral discharge; variable degree of edema and erythema
How does Urethritis affect males?
• Course: spontaneous resolution over several weeks without therapy; >95% are asymptomatic within 6 months.
• Complications:
–Epididymitis – unilateral testicular pain,
swelling
–Prostatitis – acute or chronic
How does Urogenital infections affect women?
- Asymptomatic in many
- Symptoms range from minimal to severe
- Increased vaginal discharge due to endocervical infection
- Dysuria – urethral colonization is present in 70-90% of infected women
What are the complications of Salpingitis?
- 10-20% of infected women
- Symptoms: lower abdominal pain, abnormal menses
- Can result in inflammation of fallopian tube, with scarring
- Important cause of infertility, ectopic pregnancy
What is disseminated gonohrea?
• Occurs in 0.5-3% of untreated patients
• Manifested by acute arthritis –
dermatitis syndrome
• More common in females- may be associated with recent menstruation
How is Gonorrhea dx?
- NA amplification test in urine (w/ CT)
- Gram stain (G-) sensitive in male. Diplococci
- Cx using Thayer-Martin media
How is gonorrhea treated?
• Combination treatment: Ceftriaxone 250 mg IM PLUS Azithromycin 1g PO or Doxycycline 100 mg PO, twice daily X 7 days
What are some distinguishable features of N Meningitidis?
- Commonly carried in nasopharynx as a commensal
- Sometimes causes disease
- Semi-typical gram negative cell wall
- Same as N. gonorrhoeae except that N. meningitidis has a polysaccharide capsule
What antigens are found on N meningitidis?
• Major antigens are capsular polysaccharide (CPS), LOS, pili, OMP’s
-Antigenic diversity due partly through interspecies gene exchange
How are capsule regulated?
Capsule expression is down-regulated during carriage; up-regulated during invasion into bloodstream
Which serotypes of Meningitidis cause the most infections in industrialized countries?
-B and C, recent clustered outbreaks of Y
What is the asymptomatic carriage of Meningococci?
- 10-20% of individuals carry meningococci in throats
- More common in adolescents, young adults
- Usually transient: 75% clear within a few months
- Serve as the primary reservoir of infection via droplets
- Carriage is immunizing
What is the immune response of MC?
-Maternal abx will protect you when you are born, but it will decrease and you will have to start to make your own.
What is the pathogenesis of MC?
Attachment to oropharynx – via pili
Most organisms remain as extracellular
adherent pathogens
Dissemination from pharynx is via blood stream; invasion through blood brain barrier.
What is the pathogenesis and immune response of MC?
- Susceptibility to infection is due to lack of bacteridical antibodies directed against Por, Opc, LOS.
- Opsonic antibodies develop during carriage of N. lactamica and other cross-reactive organisms in childhood
- Bactericidal antibodies develop during asymptomatic carriage of N. meningitidis.
What is the meningitis belt?
-Region in Africa where there are seasonal outbreaks, 10 % of infected die. Usually form Type A.
What are the type of vaccines for Meningococcus?
- CPS vaccines -effective against A, C, Y and W
- Group B CPS is poorly immunogenic
- MenB OMV vaccines are effective, targets PorA.
What are some clinical spectrum and manifestations of MC?
• Meningitis
• Meningococcemia
Fulminant Meningococcemia
What are sx of Meningitis?
– Seen primarily in children 6 months – 10 years
– Fever, vomiting, headache, confusion
-Maybe hearing loss
What are sx of Meningococcemia?
– Abrupt onset of illness: spiking fever, chills, arthralgias, myalgias
– 75% develop petechial rash
What are the sx of Fulminant Meningococcemia?
◦ Seen in 10-20% of patients (high levels of
endotoxin circulating)
◦ LOS induces TNF and interleukins, leading to shock, hemorrhages of skin and organs, and influx of leukocytes (meningitis)
◦ 40-60% mortality
◦ Dramatic: healthy death in 6 hours
How is MC dx?
• Gram stain of CSF (85% sensitivity)
• Culture from blood, CSF; less
commonly from skin lesions, joints
• PCR for Neisseria meningitidis is most sensitive
What is the treatment for MC?
- Penicillin G is drug of choice; adjunct steroid therapy is beneficial in children
- Alternatives include newer cephalosporins
- Antibiotic treatment of carrier state not warranted
What is the type of binding from Opa?
• Promiscuous binding
–Cell surface proteoglycans
–Extracellular matrix proteins
–Other cell surface adhesion molecules
