NEISSERIACEAE AND MORAXELLA CATARRHALIS

• The genus Neisseria contains the two gram-negative cocci established as human pathogens: Neisseria meningitidis (meningococcus), a major cause of bacteremia, and Neisseria gonorrhoeae (gonococcus), the cause of gonorrhea
• Neisseria found in animals

  • N. canis
  • N. weaveri
  • N. denitrificans
  • N. animalis
  • N. caviae
  • N. ovis
  • N. cuniculi
• Neisseriae


  • Gram-negative, whose adjacent sides are flat or concave giving them "kidney- or coffee bean–shaped" appearance; approximately 0.8 µm in diameter
  • Usually occurs in pairs (diplo-)
  • N. elongata subspecies are medium-to-large, plump rods that sometimes occur in pairs or short chains
  • Non-motile
  • Non-spore-formers
  • Aerobic/Facultative anaerobic
  • Most are capnophilic (5% CO2)
  • Grow best in a moist environment
  • Pathogens do not survive long in the environment where hostile conditions of drying, cold, acidity, or light prevail
  • Catalase-positive (EXCEPT: N. elongata subspecies)
  • Oxidase-positive
  • Most oxidize carbohydrates producing acids, but NOT gas
  • Produce autolytic enzymes that result in rapid swelling and lysis in vitro at 25°C and alkaline pH
• Habitat and transmission


  Not considered normal flora. Only found on the mucous membranes of the genitourinary tract, rectum, throat, and eye at the time of infection. Transmission is primarily by direct contact (sexually or perinatally).

  
• Gonorrhea


  A sexually transmitted infection (STI) that involves invasion of the mucous membranes of the genital tract, rectum, and throat
• Pathogenesis and clinical manifestations of gonorrhea


  1. Genital gonorrhea (salpingitis, Fitz-Hugh Curtis Syndrome)

  2. Extragenital gonorrhea (oropharyngeal, anorectal, ocular)

  3. Gonococcal bacteremia (disseminated gonococcal infection)

  4. Gonococcal ophthalmia neonatorum

  5. Other infections (endocarditis, meningitis, eye infections in adults)
• Genital gonorrhea in males

  • Primary site of infection is the urethra, with symptoms including urethritis, dysuria, and purulent urethral discharge
  • Untreated can lead to sterility
• Genital gonorrhea in females

  • Primary site of infection is the endocervix, with concomitant urethral infection, symptoms include endocervicitis, dysuria, purulent cervicovaginal discharge, menorrhagia, and dyspareunia
  • Untreated can lead to pelvic inflammatory disease (PID) and salpingitis, which may cause infertility
• Extragenital gonorrhea


  • Oropharyngeal infection seen in MSM and women with orogenital contact
  • Anorectal infection seen in MSM and women with perianal contamination
  • Ocular infection from self-inoculation of eyes from genital secretions
• Gonococcal bacteremia (disseminated gonococcal infection)


  • Results from the spread of gonococci into the bloodstream, associated with AHU strains, can cause tenosynovitis and skin lesions
• Gonococcal ophthalmia neonatorum


  • Infection of the eye in newborns acquired during passage through the birth canal, can rapidly progress to blindness if untreated
• Virulence factors of Neisseria gonorrhoeae

  • Pili
  • Outer membrane proteins (Protein I, Protein II, Protein III)
  • Endotoxin (lipooligosaccharide)
  • IgA1 protease
  • Beta-lactamase
• Pili


  • Major virulence factor, enhance attachment and resistance to phagocytosis, undergo antigenic variation
• Outer membrane proteins


  • Protein I (Por proteins) protects from immune response and serum complement
  • Protein II (Opa proteins) facilitates adherence to cells
  • Protein III (Rmp) blocks bactericidal effects of antibodies
• Endotoxin (lipooligosaccharide)


  • Undergoes antigenic variation, associated with toxicity and mucosal damage
• IgA1 protease


  • Allows attachment to mucosal surfaces by inactivating IgA1
• Beta-lactamase


  • Confers resistance to certain antibiotics
• Neisseria gonorrhoeae


  • Does not display antigenic variability
  • Stimulates the production of weak antibodies
  • Diminishes the bactericidal effects of normal human serum by inducing antibodies that block bactericidal antibodies directed against other surface antigens (Por and LOS - lipooligosaccharide)
• Outer membrane proteins of Neisseria gonorrhoeae

  • Protein I (Por proteins)
  • Protein II (Opa proteins)
  • Protein III (Rmp)
• Protein I (Por proteins)

  Protects from the host's immune response, including serum complement-mediated cell death
• Protein II (Opa proteins)


  Facilitates adherence to phagocytic and epithelial cells
• Protein III (Rmp)


  Blocks the bactericidal effect of host IgG
• Endotoxin (Lipooligosaccharide or LOS)


  • Does not have an O polysaccharide side chain
  • Undergoes antigenic variation
  • Associated with toxicity in gonococcal infections
  • Causes ciliary loss and mucosal cell death
• IgA1 protease


  Allows attachment to host mucosal surfaces by splitting and inactivating IgA1, the major mucosal immunoglobulin of humans
• β-lactamase


  Plasmid-mediated production responsible for penicillin resistance
• PPNG = penicillin-producing N. gonorrhoeae
• Ways to reduce the occurrence of gonorrhea


  • Avoiding multiple sexual partners
  • Rapid eradication of gonococci from infected individuals by means of early diagnosis and treatment, and case finding
  • Education and screening of populations at high risk
  • Use of mechanical prophylaxis such as condoms (only provides partial protection)
  • Chemoprophylaxis (of limited value because of antibiotic resistance)
• Gonococcal ophthalmia neonatorum was previously prevented by instillation of silver nitrate solution to the conjunctiva of newborns (Crede's Method), but its use has largely been replaced by local application of 0.5% erythromycin or 1% tetracycline ointment
• Humans are the only natural hosts for whom meningococci are pathogenic
• Habitat of Neisseria meningitidis

  The human nasopharynx; may form part of the transient flora of the nasopharynx without producing symptoms
• Transmission of Neisseria meningitidis


  Direct contact, inhalation of respiratory secretions or droplets
• Meningococcemia (meningococcal bacteremia)


  1. Presence of meningococcus in the bloodstream

  2. Results from the entry of meningococci from the nasopharynx into the blood stream probably by way of the cervical lymph node

  3. Symptoms: Abrupt onset with fever, chills, malaise, prostration, and petechiae on the trunk and appendages
• Purpura fulminans


  • Ecchymoses (larger form of petechiae)
  • Disseminated intravascular coagulation (DIC)
  • Shock
  • Coma
  • Waterhouse-Friderichsen Syndrome (acute hemorrhage into the adrenal glands, resulting in death in 6-8 hours)
• Meningococcal meningitis


  1. Usually associated with epidemic meningitis

  2. Second most common cause of bacterial meningitis in adults

  3. May occur simultaneously with meningococcemia, but meningitis alone occurs most frequently

  4. Symptoms: Sudden onset of fever, intense headache, stiff neck, convulsion, vomiting, progressing to coma within a few hours
• Virulence factors of Neisseria meningitidis

  • Capsule
  • Pili
  • Endotoxin
  • IgA1 Protease
• Capsule


  • The primary virulence factor of meningococci associated with blood stream invasion
  • Enables meningococci to resist the bactericidal activity of the complement and prevents destruction of the organism by phagocytes
  • Consists of polysaccharide with 13 serogroups, the most important being A, B, C, X, Y, and W-135
• Pili


  • Protrudes through the organism's capsule
  • Mediates initial attachment to surface proteins on non-ciliated cells in the nasopharyngeal epithelium of the host
  • Aggregates the meningococcal cells into microcolonies allowing attachment to epithelial microvilli and entry into the bloodstream

  
• Endotoxin (Meningococcal lipooligosaccharide or LOS)


  • Responsible for many of the toxic effects found in meningococcal disease
  • Results in vascular damage and eventually hemorrhage when shed into the generalized circulation
• IgA1 Protease


  • Allows attachment to host mucosal surfaces by splitting and inactivating IgA1, a major mucosal immunoglobulin of humans
  • Neutralizes the protective action of the mucosal immunoglobulin IgA thus facilitating attachment of the meningococci to host mucous membranes, thereby initiating infection
• Meningococcal serogroups responsible for most human infections

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