NEISSERIACEAE

Neisseria gonorrhoeae
Neisseria meningitidis
Physiology and Structure
• Gram negative coccoid, arranged in diplococcic  “coffee bean”
• Oxidase (+), >> catalase (+)
• Growth on media:
• Nonpathogenic strains: grow in blood agar & nutrient agar
• N. meningitidis: grow in blood agar, variable in nutrient agar
• N. gonorrhoeae: need supplemented media (chocolate agar, Thayer Martin)
• Temperature: 35-37 C
• Microaerophilic (need 5% CO2)
Virulence Factors
• Capsule
• N. meningitidis: polysaccharide capsule  used for serogrouping
6 serogroup (A, B, C, W135, X, Y) cause endemic and epidemic disease
• N. gonorrhoeae: no true capsule, but capsule-like negative charge
• Pili
• For attachment to host cells, genetic material transfer, motility, resistance
from neutrophile killing
• Composed of repeating protein subunits called pilins
• In N. gonorrhoeae, antigenic variation of pilins  no immunity to reinfection
& difficulty developing vaccine
Virulence Factors
• Porin proteins
• Integral protein in outer membrane  for influx nutrient and efflux waste
• Two gene: PorA, PorB
• N. meningitidis expresses both, N. gonorrhoeae only PorB
 PorB is needed for gonococci for survival  logical target for vaccine
 BUT there are PorB1A and PorB1B & >>> serologic variant  difficult
• PorB in gonococci
Interfere neutrophile degranulation
Protect from inflammatory response
Help adhere with host epithelial cells
Resistance from complement-mediated serum killing
Virulence Factors
• Opa proteins (opacity proteins)
• Firm and strong attachment to epithelial and phagocytic cells
• Cell to cell signalling
• Gonococci expressing Opa  appear opaque in culture (mostly for localized
disease)
• Rmp protein (reduction-modifiable protein)
• Protect other surface antigens from serum bactericidal
• With porins  forming pores
• Iron complex binding protein
• Iron acquisition  specific to human iron complex
• Transferrin-binding protein, lactoferrin-binding protein, hemoglobin-binding
protein
Virulence Factors
• Lipooligosaccharide (LOS)
• Just like LPS (lipopolysaccharide) (has Lipid A and oligosaccharide core), but
no O-antigen polysaccharide
• Lipid A  endotoxin
• During rapid proliferation  release of outer membrane blebs (contains LOS
and other surface antigens)  endotoxin activity & protects bacteria from
antibodies targeting surface antigens
• IgA1 protease  Cleaves hinge region of IgA1  inactive
• β lactamase  degrades penicillin
Pathogenesis
• N. gonorrhoeae
• attach and penetrate mucosal cells  mediated by pili, PorB, and Opa
• LOS  endotoxin  stimulate TNF-α  systemic symptoms
• Immunity: IgG3 against pilin, Opa, LOS
• Antibody against LOS  activate complement  neutrophil chemotactic
• IgG and sIgA against Rmp  blocks the antibody response
Pathogenesis
• N. meningitidis
• Attach to nonciliated cells of nasopharynx
• Capsule interfere attachment  downregulated before attachment
• Multiplication and adhesion of aggregates in the host cell
• Posttranslational modification of pili  destabilize of aggregates  bacteria can
penetrate to deeper tissue, and release into airway  person to person spread
• Capsule: protects from phagocyte destruction
• LOS endotoxin  diffuse vascular damage (endothelial damage, thrombosis)
• Immunity: antibodies against polysaccharide capsule, complement
• Infants have protective antibody from mother, but decreasing in 6 months
• Deficiencies of C5, C6, C7, C8 increase risk 6000 fold
Epidemiology
• Gonorrhea
• Only in human, 2nd most common STI after chlamydia
• Transmission: sexual contact
• > 50% women have mild or asymptomatic, but nearly all men symptomatic
• Problem: asymptomatic carrier after the symptoms generally clear by itself
• Endemic Meningococcal disease
• Of 13 serogroup: A, B, C, W135, X, Y are the most common
• Transmission: respiratory droplets among people close contact
• Asymptomatic carriage: >> in school age children, young adult, cold season
• Disease: >> children < 5 yr old (<6 months), teenager, young adult,
• Prone to infection in epidemics: Immunocompromised, elderly, closed population
Clinical Diseases-N. gonorrhoeae
• Gonorrhea
• Men
• Mostly in urethra  urethritis (purulent discharge, dysuria)
• Incubation 2 – 5 days
• Complication rare: epididymitis, prostatitis, periurethral abscess
• Women
• Mostly in cervix (endocervical columnar epithelial cells)
• Vaginal discharge, dysuria, abdominal pain
• Complication: salpingitis, PID
Clinical Diseases-N. gonorrhoeae
• Gonococcemia
• Mostly in untreated infection in women
• Disseminated infection  septicemia, arthritis, dermatitis
• Fever, migratory arthralgia, suppurative arthritis, pustular rash with
erythematous base
• Other
• Perihepatitis (Fitz-Hugh-Curtis syndrome)
• Ophthalmia neonatorum (newborns infected during vaginal delivery)
• Anorectal gonorrhea in homosexual men
• Pharyngitis gonorrhea
Clinical Diseases-N. meningitidis
• Meningitis
• Headache, meningeal signs, fever  younger children non specific
(fever, vomit)
• Neurologic sequelae <<: hearing deficit, learning disabilities, arthritis
• Meningococcemia
• Thrombosis in multiple blood vessel and organ
• Small petechie  combined into hemorrhagic lesion
• DIC + shock + bilateral adrenal destruction (Waterhouse-Frederichsen
syndrome)
• Other: pneumonia, arthritis, urethritis
Laboratory Diagnosis
• Microscopy
• Gonococci:
• Gram stain: gram negative diplococcic with PMN
• Sensitive and specific in symptomatic men
• Women or asymptomatic men need confirmation
• Specific for purulent arthritis, but not with skin, anorectal, pharyngitis infection
• Meningococci
• Positive in CSF, if before antibiotic
• Overwhelming meningocococcemia positive in blood
• Antigen detection : less useful (in the past used for meningococci capsule
antigen
Laboratory Diagnosis
• Nucleic acid-based
• For combination gonococci and chlamydia  rapid, sensitive, specific
• Need confirmation for nongenital infection
• Can’t monitor antibiotic resistance
• Culture
• Specimen gonococci: urethral swab (men), endocervical swab (women), blood (in
disseminated disease), joint aspirate (arthritis)
• Specimen meningococci: CSF, blood, sputum
• Nonselective media: chocolate agar
• Selective media: modified Thayer Martin  some strains inhibited by vancomycin in this
media
• Inhibited by fatty acids & trace metals  can’t grow in blood agar and nutrient agar
• Do not survive drying and cold temperature  direct inoculation into prewarmed media
Laboratory Diagnosis
• Identification
• Preliminary pathogenic Neisseria sp.
 oxidase positive, gram negative diplococci grow in chocolate agar
or Neisseria selective media
• Carbohydrate utilization/fermentation  producing acid
• N. gonorrhoeae : glucose only
• N. meningitidis: glucose and maltose
Treatment & Prevention-N. gonorrhoeae
• Historically: penicillin
• Resistance now: penicillin, tetracycline, ciprofloxacin
• Choice: Ceftriaxone + (azithromycin OR doxycycline)
• Prevention:
• Education
• Aggressive detection
• Screening sexual contact
• Eye ointment prophylaxis for newborn (1% silver nitrate, 1% tetracycline, 5%
erythromycin)
• No chemoprophylaxis for genital infection
• No vaccine available  because of antigenic diversity
Treatment & Prevention-N. meningitidis
• Choice: cefotaxime or ceftriaxone
• Penicillin G if found susceptible
• Chemoprophylaxis
• Regimen: rifampin, ciprofloxacin, or ceftriaxone
• For person with significant exposure with meningococcal disease patients
(direct exposure with respiratory secretion OR > 8 hour close contact)
• Meningococcal vaccine
• Tetravalent vaccine (serogroup A, C, Y, W135)
• Comes in polysaccharide and polysaccharide protein conjugate vaccine
Other Neisseria sp.
Neisseria sicca and Neisseria mucosa
• Commensal organism in oropharynx
• Meningitis, osteomyelitis, endocarditis, bronchopulmonary infection,
acute otitis media, acute sinusitis
• Mostly penicillin susceptible, although some developed resistance
(caused by PBP2 expression)
Eikenella corrodens
• Small, fastidious, gram negative rods, classified as HB-1
• Non motile, non-spore forming, facultative anaerob
• Normal flora in upper resp. tract
• Clinical:
• Opportunistic in immunocompromised or oral cavity trauma
• Mostly happen in human bite wound or fistfight injury
• Other: endocarditis, sinusitis, meningitis, brain abscess
• Presumptive laboratory diagnosis: slow growing gram negative rod,
produce pit in blood agar (“corrode”), have a bleach-like odor
• Treatment: penicillin, ampicillin, extended cephalosporin, floroquinolone
Kingella kingae
• Small gram negative coccobacilli, facultative anaerob, ferments
carbohydrate, fastidious growth req.
• Clinical:
• Septic arthritis in children
• Endocarditis in all ages
• Slow growing  3 days or more incubation to be detected in specimen
• Treatment: penicillin, tetracycline, erythromycin, floroquinolone,
aminoglycoside