Neisseria gonorrhoeae, the gonococcus, is a gram-negative diplococcus that causes the sexually transmitted disease, gonorrhea. Gonorrhea commonly manifests as cervicitis, urethritis, and conjunctivitis. Neisseria gonorrhoeae is an exclusive human pathogen that primarily infects the urogenital epithelia. Urethra in male and uterine cervix in female serve as the initial sites for gonococcal infection. Other sites are conjunctiva, pharynx and rectal mucosa.
A repertoire of virulence factors has been identified in gonococci that allow the bacterium to successfully adapt to variable microenvironments in human hosts.
Pili is the principal virulence factor of gonococci. It plays a major role in adherence and also prevents bacteria from phagocytosis. It helps in the attachment of the Neisseria gonorrhoeae to microvilli of nonciliated columnar epithelial cells.
Pili are composed of pilin proteins which are antigenically distinct, undergo antigenic and phase variation that help in typing of gonococci.
Outer membrane proteins (PorB)
Major outer membrane porin (PorB) expressed by Neisseria gonorrhoeae plays multiple roles during infection, in addition to its function as an outer membrane pore. PorB is a voltage-gated pore that mediates ion exchange between N. gonorrhoeae and the environment. PorB also appears to perform multiple functions contributing to N. gonorrhoeae pathogenesis;
- induce or inhibit apoptotic signaling,
- contribute to serum resistance via interactions with regulators of the classical and alternative complement pathway,
- mediate epithelial cell invasion under low-phosphate conditions,
- can affect the generation of reactive oxygen species (ROS) by innate immune cells.
N. gonorrhoeae strains contain a single porB gene in one of two allelic forms (P.IA or P.IB), and the two alleles have been associated with different biological phenotypes. P.IA-expressing strains tend to be associated with disseminated disease, whereas P.IB-expressing isolates typically cause localized urogenital infections
Neisserial opacity (Opa) proteins
They are a family of antigenically distinct outer membrane proteins that undergo phase-variable expression. Opa proteins promote persistence of N. gonorrhoeae in the female genital tract and opa gene phase variation allows gonococci to invade human epithelial cells.
Opacity associated proteins are also responsible for the opaque nature of gonococcal colonies.
Transferrin binding proteins
Neisseria gonorrhoeae produces two transferrin binding proteins, TbpA and TbpB, which specifically bind and internalize iron from host‐derived proteins, including transferrin, lactoferrin, and haemoglobin.
Strains of N. gonorrhoeae produce two distinct extracellular IgA1 proteases that cleave the heavy chain of the human immunoglobulin IgA at different points within the hinge region. Split products of IgA1 have been found in the genital secretions of women with gonorrhea.
The lipopolysaccharide of Neisseria gonorroheae consists of only lipid A and core oligosaccharides but lacks repeating O-side chains so is referred to as lipooligosaccharide; the LPS of enteric bacteria also contains O-side chains.
Lipooligosaccharide: Lipooligosaccharide (LOS) of Neisseria gonorrhoeae activates the alternative complement pathway of the host. It has marked endotoxic activity; it stimulates the production of tumor necrosis factor (TNF) that causes cell damage.
References and further readings
- Jennifer L. Edwards, Michael A. Apicella. The Molecular Mechanisms Used by Neisseria gonorrhoeae To Initiate Infection Differ between Men and Women. Clinical Microbiology Reviews. 2004; 17 (4) 965-81; doi: 10.1128/CMR.17.4.
- Chen A, Seifert HS. Structure-function studies of the Neisseria gonorrhoeae major outer membrane porin. Infect Immun. 2013;81(12):4383–4391. doi:10.1128/IAI.00367-13
- Quillin, S., Seifert, H. Neisseria gonorrhoeae host adaptation and pathogenesis. Nat Rev Microbiol 16, 226–240 (2018). https://doi.org/10.1038/nrmicro.2017.169