Neisseria gonorrhoeae

Albert Neisser 1879; 1881 Introduction of Credé prophylaxis (1% Argentum nitricum) in newborns by the gynaecologist Karl Credé.

Neisseriagonorrhoeae (gonococci) are obligate human-specific pathogenic, gram-negative, coffee bean-shaped, paired, strictly aerobic growing diplococci in the genus Neisseria. They are catalase and cytochrome oxidase positive. Gonococci are very sensitive to environmental influences, especially to desiccation (to be taken into account in cultural detection). Neisseria gnonorrhoeae are pathogens of the sexually transmitted disease gonorrhoea. The reservoir is exclusively the infected human being.

Unlike Neisseria meningitidis, gonococci do not have a true capsule. Their membrane contains lipooligosaccharides (LOS) that can bind sialic acid, allowing them to build a capsular structure that enables serum resistance and extracellular survival in the host.

Pathogenicity factors: Gonococci effectively evade the host humoral immune response by producing a bundle of pathogenicity criteria that allow them to subvert local immune barriers (Seifert HS 2019).

These include:

• Opaque proteins (OPA =opacity, as they make colonies appear opaque). Gonococci express several different OPA proteins. These are usually not expressed at the same time. OPA proteins attach to the cell wall and are responsible for the organotropism of Neisseria gonorrhoeae. The germs bind to CD66, heparan sulfate proteoglycan receptors and CGM1 on fibroblasts, epithelial cells and macrophages via OPA proteins.
• Note: Each OPA gene has multiple repeating sequences (repeats) of 5 nucleotides. These are regularly excised or duplicated, changing the reading frame and giving rise to new variants of OPA proteins. This mechanism is called antigenic variation.
• Transporters for transferrin and lactoferrin: Transporters for transferrin and lactoferrin are found on the surface of Neisseria gonorrhoeae. For this species, iron supply is essential.
• Adhesive pili: Gonococci possess pili composed of pilin, which are important for attachment to the mucosal epithelium. The pili are also antigen variable (Hill SA et al 2009). Without pili, gonococci lose their virulence!
• Penicillinase: Some strains of Neisseria gonorrhoeae produce a mostly plasmid-encoded penicillinase and thus become penicillin resistant.
• IgA1 protease: The enzyme IgA1 protease produced by Neisseria gonorrhoeae is capable of cleaving IgA antibodies. Thus, gonococci override an important defense mechanism of the mucous membranes. The IgA1 protease cleaves the constant Fc part of the antibody from the antigen-binding part, Fab fragment. The Fc fragment serves to bind to the Fc receptor of phagocytosing cells. Since the Fab fragment nevertheless binds specifically to the epitopes of the bacteria, the bacteria are masked by these endogenous proteins and are no longer recognised as foreign by the defence cells(antigen mimicry). This also explains the tendency for the infection to become chronic.
• Lipoligosaccharides: Lipoligosaccharides on the bacterial surface have a damaging effect on the epithelial cell, condition the antigenicity and form capsule-like structures by binding sialic acid, which inhibit the complement effect. Specifically, sialic acid (N-acetyl-neuraminic acid) binds protein H, degrades C3b, and thereby escapes attack by complement MAC.
• Endotoxin: Endotoxin located in the outer membrane induces a violent inflammatory structure.

S.u. Clinic

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2. Eyre DW et al. (2018) Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018.Euro Surveill 23(27).
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7. Unemo M et al. (2011) Review and international recommendation of methods for typing neisseria gonorrhoeae isolates and their implications for improved knowledge of gonococcal epidemiology, treatment, and biology. Clin Microbiol Rev 24:447-458.
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9. Whiley DM et al. (2018) Genetic characterisation of Neisseria gonorrhoeae resistant to both ceftriaxone and azithromycin. Lancet Infect Dis18:717-718.
10. World Health Organization (WHO) 1990. global surveillance network for gonococcal antimicrobial susceptibility Geneva: WHO; 1990. WHO/VDT/90-452. available from: http://apps.who.int/medicinedocs/documents/s16348e/s16348e.pdf6