Neisseria gonorrhoeae

*Neisseria gonorrhoeae* (singular: gonococcus, plural: gonococci) is a Gram-negative, oxidase-positive, microaerophilic bacterium that was first isolated in 1879 by Albert Neisser. As an obligate human pathogen, it mainly infects the mucosal surfaces of the urogenital tract but can also attach to the linings of the nose, pharynx, rectum, and conjunctiva. The organism is responsible for the sexually transmitted infection gonorrhea, as well as other conditions such as disseminated gonococcemia, septic arthritis, and gonococcal ophthalmia neonatorum.

This bacterium can survive being engulfed by phagocytes and even multiply inside neutrophils. To culture it in the lab, carbon dioxide supplementation and enriched agar (like chocolate agar) are required, often with antibiotics such as those in Thayer–Martin medium. *N. gonorrhoeae* evades the immune system through antigenic variation, achieved by genetically recombining its pili and surface proteins.

Sexual transmission occurs via vaginal, anal, or oral sex and can be prevented with barrier protection. Perinatal transmission during childbirth is also possible, but this can be avoided by treating the mother with antibiotics before delivery and applying antibiotic eye gel to the newborn. Infection does not confer protective immunity, so people can be reinfected multiple times—a risk heightened by the bacterium’s ability to alter its surface proteins and evade immune detection.

Asymptomatic infections are common in both men and women. If left untreated, the infection can spread throughout the body (disseminated gonococcal infection), particularly to the joints (septic arthritis). In women, untreated infection may lead to pelvic inflammatory disease and potential infertility due to scarring. Diagnosis is made via culture, Gram staining, or nucleic acid tests (such as polymerase chain reaction) on urine, urethral swabs, or cervical swabs. Because co-infection with chlamydia and other STIs is common, testing for those is also recommended.

Antibiotic resistance in *N. gonorrhoeae* is an increasing public health concern, as the bacterium readily develops resistance. This ability to quickly adapt to new antimicrobials has been observed repeatedly since the 1930s, rendering many treatment regimens obsolete. Some strains have already shown resistance to the current standard treatment, ceftriaxone.

**Microbiology** *Neisseria* species are fastidious, Gram-negative cocci (though some are rod-shaped and appear in pairs or short chains) that need nutrient supplementation to grow in culture. They are facultative intracellular pathogens, able to persist inside host cells but also multiply outside them. They typically appear as coffee-bean-shaped diplococci. Members of this genus do not form endospores and are nonmotile, except for pathogenic species, which use twitching motility; most are obligate aerobes. Of the 17 *Neisseria* species that colonize humans, only two are pathogenic: *N. gonorrhoeae* (causing gonorrhea) and *N. meningitidis* (a major cause of bacterial meningitis).

**Culture and identification** *N. gonorrhoeae* can be isolated on Thayer–Martin agar (or VPN agar) in an atmosphere enriched with 3–7% carbon dioxide. Thayer–Martin agar is a chocolate agar plate (heated blood agar) containing nutrients and antimicrobials (vancomycin, colistin, nystatin, and trimethoprim) that promote *Neisseria* growth while suppressing contaminating bacteria and fungi. Martin Lewis agar and New York City agar are other selective chocolate agars commonly used. The bacterium is oxidase positive (it has cytochrome c oxidase) and catalase positive (it converts hydrogen peroxide to oxygen). When tested with the carbohydrates lactose, maltose, sucrose, and glucose, *N. gonorrhoeae* oxidizes only glucose.

**Metabolism** *Carbon* Unlike other *Neisseria* species that can also metabolize maltose, *N. gonorrhoeae* uses only glucose, pyruvate, and lactate as central carbon sources. Glucose is catabolized via both the Entner–Doudoroff (ED) and pentose phosphate (PP) pathways, with the ED pathway being the primary oxidative route. These pathways are essential because *N. gonorrhoeae* lacks the phosphofructokinase (PFK) gene and therefore cannot use the Embden–Meyerhof–Parnas (EMP) pathway for glucose catabolism. However, it does have the enzyme fructose 1,6-bisphosphatase, allowing gluconeogenesis.

Glucose is first metabolized through the ED pathway to produce pyruvate and glyceraldehyde 3-phosphate. The latter is then further processed by EMP pathway enzymes to yield another pyruvate molecule. These pyruvate molecules are converted into acetyl-CoA, which enters the citric acid cycle (CAC) to generate high-energy electron carriers for ATP production via the electron transport chain. However, the CAC is mainly used for producing biosynthetic precursors rather than for catabolism. This is partly because several CAC enzymes—citrate synthase, aconitase, and isocitrate dehydrogenase—are expressed at low levels in the presence of glucose, pyruvate, or lactate. Instead, a partial CAC operates: α-ketoglutarate is formed by glutamate dehydrogenase or by transamination of oxaloacetate and glutamate (via aspartate aminotransferase, yielding aspartate and α-ketoglutarate). The cycle then continues from α-ketoglutarate to produce oxaloacetate, an important precursor for various biosynthetic pathways. Another distinctive feature of the gonococcal CAC is the absence of malate dehydrogenase, which prevents the full cycle from completing.