Neisseria: Gram-Negative Cocci (Ditki Notes)

• Neisseria are Gram-negative cocci that often appear in pairs, resembling coffee beans.
• They are catalase and oxidase positive, which means they produce catalase to protect against self-induced oxidative damage.
• Pathogenic Neisseria use type IV pili for twitching motility and can invade host cells.

Overview

• Neisseria meningitidis, also known as meningococcus, includes pathogenic serogroups A, B, C, Y, and W-135, each responsible for geographically distinct epidemics and can grow on both chocolate and blood agar.
• Neisseria gonorrhoeae, also known as gonococcus, requires highly specific growth conditions and grows only on chocolate agar and can be isolated using selective Thayer-Martin chocolate agar with antibiotics.

Neisseria Virulence Factors

• Virulence factors are located in the cell wall.
• Neisseria endotoxin consists of Lipooligosaccharide (LOS) that contains toxic lipid A.
• Neisseria releases "blebs" of cell membranes containing endotoxin during infection.
• Pili is a key colonization step that attaches to host cells and resists neutrophil bactericidal activities.
• Type IV pili is used for twitching motility.
• IgA1 protease degrades Immunoglobulin A, helping the bacteria reach mucous membranes of the respiratory and genital tracts.
• Neisseria uses special receptors to bind host transferrin, lactoferrin, and hemoglobin to acquire iron.
• Opacity proteins (Opa) bind epithelial and phagocytic cells, engaging in cell to cell signaling.
• Reduction-modifiable proteins (Rmp) protect porin and lipooligosaccharide from bactericidal antibodies.
• Porin proteins (Por) create pores in bacterial cells allowing nutrients and wastes to pass and they also prevent phagolysosome fusion in neutrophils, and aid in intracellular survival thus invasion of epithelial cells.
  • PorA is active only in Neisseria meningitidis.
  • PorB is active in both N. meningitidis and N. gonorrhoeae.
• Opa, Por and Rmp proteins are outer membrane protein classes I-V in Neisseria meningitidis.
  • Outer polysaccharide capsule in Neisseria meningitidis allows the bacteria to resist phagocytosis.
  • Vaccines use this capsule as an immunogen, it is not effective for Group B meningococcus because its capsule is not immunogenic.
  • Factor H binding protein (FHBP) binds Factor H to inhibit complement factor C3b which inhibits opsonization and membrane attack complex formation, is present on Group B meningococci, and is used as a vaccine immunogen.
• Some strains of Neisseria gonorrhoeae produce beta-lactamase (penicillinase) to promote penicillin resistance.

Neisseria Meningitidis

• Transmitted in airborne respiratory droplets, after entry pili and other adhesins promote adherence to the pharynx leading to bloodstream.
• Individuals with complement deficiencies are at risk for meningococcal disease.
• Some people are chronic carriers that can spread infection.
• Meningococcal diseases are preventable with vaccines, Infections can be treated with Cephalosporin or Penicillin G.
• Meningitis is inflammation of the meninges that cover the brain and/or spinal cord, which is most commonly caused by Neisseria meningitidis in individuals ages 2-18, Streptococci pneumoniae is also a major cause.
  • Patients have fever, stiff neck, headache, and increased neutrophils in their cerebrospinal fluid.
• Meningococcemia is the presence of Neisseria meningitidis in the blood with or without meningitis, which is characterized by fever, headache, nausea, vomiting, and chills.
  • Skin lesions start as small petechiae-like spots that coalesce into larger hemorrhagic areas.
  • Vascular damage can lead to gangrene.
  • Musculoskeletal pain is common.
  • Adrenal gland hemorrhage (Waterhouse-Friderichsen syndrome) and thrombosis with vessel and organ damage can be fatal.
  • Pneumonia can occur, particularly in older adults.

Neisseria Gonorrhoeae

• There is no vaccine.
• Sexually transmitted, causing local infections of the genitals, rectum, and pharynx; within the blood, it causes disseminated infection.
• Asymptomatic carriers are a key reservoir.
  • In males, the most common site of infection is the urethra; purulent discharge is common with complications of epididymitis, prostatitis, and development of periurethral abscesses.
  • In females, the cervix is the primary site of infection, many women are asymptomatic however can experience cervical discharge, abdominopelvic pain, and bleeding.
    • Complications occur when infection ascends to the uterus and uterine tubes, resulting in pelvic inflammatory disease, where ectopic pregnancies and infertility occur as a result of scarring.
• Opthalmia neonatorum occurs when mothers pass gonorrheal infection to offspring during passage through the birth canal; leading affected neonates to acquire opthalmia neonatorum, which is a form of conjunctivitis that can be prevented with prophylactic use of erythromycin ointment shortly after birth.
• Systemic gonococcemia produces fever, chills, and skin pustules on the extremities and septic arthritis.