Table of Content:
- Introduction to Genus Neisseria
- Introduction to Neisseria gonorrhoeae
- Virulence Factors of Neisseria gonorrhoeae
- Pathogenesis of Neisseria gonorrhoeae
- Disease Manifestation of Neisseria gonorrhoeae
- Host Defenses of Neisseria gonorrhoeae
- Treatment of Neisseria gonorrhoeae
- Introduction to Neisseria meningitidis
- Virulance Factors of Neisseria meningitidis
- Pathogenesis of Neisseria meningitidis
- Disease manifestation of Neisseria meningitidis
- Host Defences of Neisseria meningitidis
- Treatment of Neisseria meningitidis
Introduction to Genus Neisseria
Morphology
- Members of the genus Neisseria are Gram-negative bacteria.
- They appear as bean-shaped diplococci when observed under the microscope.
- None of the species develop flagella or spores.
- Pathogenic species of Neisseria possess capsules, which contribute to their virulence.
- They also have pili, which aid in attachment and colonization.
Physiology
- Neisseria species are strict parasites and do not survive long outside of the host.
- They are aerobic or microaerophilic in nature.
- Their metabolism is oxidative.
- They produce both catalase and cytochrome oxidase enzymes.
- Pathogenic species require enriched complex media, such as chocolate agar or modified Thayer-Martin medium, and also need the presence of CO₂ for growth.
- Neisseriae are Gram-negative cocci that usually occur in pairs.
- Two important pathogenic species include:
- Neisseria gonorrhoeae (gonococci)
- Neisseria meningitidis (meningococci)
- These species are pathogenic for humans and are typically found associated with or inside polymorphonuclear cells.
- Individual cocci are kidney-shaped; when they occur in pairs, the flat or concave sides of the cells are adjacent.
Cultural characteristics
- In 48 hours of incubation on enriched media, Neisseria species develop visible colonies.
- Commonly used enriched media include:
- Modified Thayer-Martin Agar
- Martin-Lewis Agar
- New York City medium
- The colonies produced are transparent or opaque, nonpigmented, and nonhemolytic.
- Meningococci and gonococci grow best on media that contain complex organic substances, such as heated blood, heme, and animal proteins.
- Optimal growth also requires an atmosphere containing about 5% CO₂, which can be provided using a candle jar.
Introduction to Neisseria gonorrhoeae
- Neisseria gonorrhoeae possesses a typical Gram-negative outer membrane that is composed of proteins, phospholipids, and lipopolysaccharide (LPS).
- The neisserial LPS is different from enteric LPS because:
- It has a highly branched basal oligosaccharide structure.
- It lacks repeating O-antigen subunits.
- Due to these differences, the LPS of Neisseria is referred to as lipooligosaccharide (LOS).
- N. gonorrhoeae is a relatively fragile organism, making it highly susceptible to temperature changes, drying, UV light, and other environmental stresses.
- Strains of N. gonorrhoeae are fastidious and variable in their cultural requirements, requiring media with specific supplements such as hemoglobin, NAD, yeast extract, and other nutrients for successful isolation and growth.
- Cultures of N. gonorrhoeae are grown at 35–36°C in an atmosphere enriched with 3–10% added CO₂.
Virulence Factors of Neisseria gonorrhoeae
The first stages of infection in gonococci, including adherence and invasion, are mediated by surface components of the bacteria.
Pilli (Fimbriae):
- These are hair-like appendages that extend up to several micrometers from the gonococcal surface.
- They play a role in enhancing attachment to host cells and provide resistance to phagocytosis.
- Pili are composed of stacked pilin proteins.
Por Protein (Porin):
- This protein extends through the gonococcal cell membrane.
- It exists as trimers that form pores in the surface, allowing some nutrients to enter the cell.
Opa Proteins:
- These proteins function in adhesion of gonococci within colonies.
- They also facilitate attachment of gonococci to host cell receptors.
IgA1 Protease:
- This enzyme splits and inactivates IgA1, which is the major mucosal immunoglobulin of humans, aiding in immune evasion.
Pathogenesis of Neisseria gonorrhoeae
- The bacteria adhere to columnar epithelial cells, then penetrate them and multiply on the basement membrane.
- Adherence is mediated by pili and Opa proteins.
- During infection, lipooligosaccharide (LOS) and peptidoglycan are released as a result of autolysis of bacterial cells.
- Both LOS and peptidoglycan activate the host’s alternative complement pathway.
- LOS also stimulates the production of tumor necrosis factor (TNF), which contributes to cell damage.
- Ocular infections caused by N. gonorrhoeae can lead to serious complications, including corneal scarring or perforation.
- A specific ocular infection, ophthalmia neonatorum, occurs most commonly in newborns who are exposed to infected secretions in the birth canal.
- To prevent such ocular infections, silver nitrate or an antibiotic is routinely applied to the eyes of newborns.
Disease Manifestation of Neisseria gonorrhoeae
- In males, signs of disease include:
- Purulent discharge in cases of urethritis.
- The organism may invade the prostate, leading to prostatitis.
- Infection may extend to the testicles, resulting in orchitis.
- In females, manifestations include:
- Cervical involvement that can extend through the uterus to the fallopian tubes, causing salpingitis.
- Infection may also spread to the ovaries, resulting in ovaritis.
- Up to 15% of women with uncomplicated cervical infections may develop pelvic inflammatory disease (PID).
- The involvement of testicles, fallopian tubes, or ovaries may lead to sterility.
Host Defenses of Neisseria gonorrhoeae
- Infection with N. gonorrhoeae stimulates inflammation and a local immune response, particularly involving IgA.
- While inflammation helps to focus host defenses, it also contributes significantly to the pathology of the disease.
- Nonspecific factors play a role in natural resistance to gonococcal infection.
- In women, resistance may increase at certain times of the menstrual cycle due to changes in genital pH and hormone levels.
- Urine contains both bactericidal and bacteriostatic components effective against N. gonorrhoeae.
- Important urinary factors influencing resistance include pH, osmolarity, and the concentration of urea.
Treatment of Neisseria gonorrhoeae
- The currently recommended antimicrobial agents for treating Neisseria gonorrhoeae infections include:
- Ceftriaxone
- Cefixime
- Ciprofloxacin
- Ofloxacin
- Cephalosporins remained the foundation of gonorrhea treatment according to the 2010 CDC STD treatment guidelines.
Introduction to Neisseria meningitidis
- Neisseria meningitidis is usually cultivated in a peptone-blood base medium within a moist chamber containing 5–10% CO₂.
- The bacterium possesses a prominent antiphagocytic polysaccharide capsule, which serves as a major virulence factor.
- N. meningitidis tends to colonize the posterior nasopharynx of humans, and humans are the only known host.
- Individuals who are colonized act as carriers of the pathogen and can transmit disease to nonimmune individuals.
- During the early stages of infection, the bacterium colonizes the posterior nasopharynx before it invades the meninges.
- The only distinguishing structural feature between N. meningitidis and N. gonorrhoeae is the presence of a polysaccharide capsule in N. meningitidis.
- The capsule is antiphagocytic and is crucial in pathogenesis.
- The term meningitis refers to inflammation of the meninges of the brain or spinal cord.
- Meninges are the three membranes that envelope the brain and spinal cord.
- The disease meningitis can be caused by several different bacteria and viruses, including N. meningitidis.
Virulance Factors of Neisseria meningitidis
- The major toxin of Neisseria meningitidis is its lipooligosaccharide (LOS), which acts through an endotoxic mechanism.
- An important determinant of virulence is the antiphagocytic polysaccharide capsule, which protects the bacterium from host immune defenses.
- Attachment to host cells is primarily mediated by fimbriae, and possibly also by other outer membrane components.
Pathogenesis of Neisseria meningitidis
- Infection occurs through aspiration of infective bacteria, which attach to epithelial cells of the nasopharyngeal and oropharyngeal mucosa.
- The bacteria then cross the mucosal barrier and enter the bloodstream.
- The mildest form of disease is a transient bacteremic illness, characterized by:
- Fever
- Malaise
- Symptoms usually resolve spontaneously within 1–2 days.
- The most serious form is the fulminant form, which is complicated by meningitis.
- The clinical manifestations of meningococcal meningitis are similar to those of acute bacterial meningitis caused by organisms such as:
- Streptococcus pneumoniae
- Haemophilus influenzae
- Escherichia coli
- Common symptoms include:
- Chills
- Fever
- Malaise
- Headache
- In addition, signs of meningeal inflammation are present.
Disease manifestation of Neisseria meningitidis
- Neurologic signs are common in meningococcal disease.
- About one-third of patients present with convulsions or coma at the time of first medical examination.
- Signs of meningeal irritation are frequently observed, including:
- Spinal rigidity
- Hamstring spasms
- Exaggerated reflexes
- Fulminant meningococcemia occurs in 5–15% of patients with meningococcal disease and is associated with a high mortality rate.
- The condition begins abruptly with:
- Sudden high fever
- Chills
- Myalgias (muscle pain)
- Weakness
- Nausea and vomiting
- Headache
- Within a few hours, patients may also develop:
- Apprehension
- Restlessness
- Delirium
Host Defences of Neisseria meningitidis
- N. meningitidis establishes systemic infections only in individuals who lack serum bactericidal antibodies directed against either the capsular antigens or the noncapsular (cell wall) antigens of the invading strain.
- The integrity of the pharyngeal and respiratory epithelium is an important protective factor against the development of invasive disease.
Treatment of Neisseria meningitidis
- Penicillin is the drug of choice for the treatment of both meningococcemia and meningococcal meningitis.
