Pathogenesis and Clinical Manifestation of Neisseria gonorrhoeae


Neisseria gonorrhoeae is a gram-negative diplococcus that causes gonorrhea, a sexually transmitted infection that can affect the urethra, cervix, rectum, pharynx, and conjunctiva. Gonorrhea can lead to serious complications such as pelvic inflammatory disease, infertility, ectopic pregnancy, and disseminated gonococcal infection. The pathogenesis of Neisseria gonorrhoeae depends on its ability to evade the host immune system and to adhere to and invade the mucosal epithelial cells. To achieve this, the bacterium expresses various virulence factors or antigenic structures on its surface that mediate different aspects of infection. Some of the major virulence factors or antigenic structures of Neisseria gonorrhoeae are:

  • Pili: These are hair-like appendages that extend from the bacterial surface and facilitate the exchange of genetic material between strains and the attachment to human mucosal cells. Pili also help the bacterium to invade host cells and to resist phagocytosis by neutrophils. Pili undergo genetic and phase variation to avoid recognition by host antibodies.
  • Porin proteins (Por): These are proteins that form pores in the bacterial membrane and allow the entry of some nutrients. Por proteins also modulate the intracellular killing of gonococci by preventing the fusion of phagosomes and lysosomes within neutrophils. Moreover, Por proteins can bind to complement components C3b and C4b and confer variable resistance to serum bactericidal activity.
  • Opacity proteins (Opa): These are proteins that function in the adhesion of gonococci within colonies and in the attachment of gonococci to host cell receptors such as heparin-related compounds and CD66 or carcinoembryonic antigen–related cell adhesion molecules. Opa proteins also induce endocytosis of gonococci by host cells and contribute to tissue tropism and immune evasion.
  • Reduction modifiable protein (Rmp): This is a protein that associates with Por in the formation of pores in the cell surface. Rmp blocks the bactericidal effect of host IgG by interfering with the binding of antibodies to Por proteins.
  • Lipooligosaccharide (LOS): This is a type of lipopolysaccharide that lacks long O-antigen side chains and is composed of lipid A, core oligosaccharide, and variable terminal structures. LOS is responsible for most of the toxicity and endotoxic effects of gonococcal infections, such as fever, inflammation, tissue damage, and shock. LOS also stimulates the release of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) by host cells.
  • Other proteins: These include Lip (H8), a heat-modifiable protein that is exposed on the bacterial surface; Fbp (ferric-binding protein), a protein that is expressed when iron supply is limited and helps the bacterium to acquire iron from host sources; and IgA1 protease, an enzyme that cleaves and inactivates IgA1, a major mucosal immunoglobulin of humans.

These virulence factors or antigenic structures enable Neisseria gonorrhoeae to colonize, invade, survive, and cause damage in the human host. Understanding their roles and mechanisms is essential for developing effective strategies for prevention, diagnosis, and treatment of gonorrhea.