Neisseria gonorrhoeae: A Comprehensive Guide

There are two types of genus Neisseria: pathogenic and non-pathogenic. Neisseria gonorrhoeae is a pathogenic gram-negative bacterium that is responsible for causing gonorrhea.

It was named after a scientists Albert Neisser, who discovered the etiological agent of gonorrhea in the pus of patients in 1889. But the bacterium was first discovered in 1979 by a German physician Albert Ludwig Sigesmund. Gonorrhea is a sexually transmitted infection (STI) and the causative agent of it is Neisseria gonorrhoeae, which is an obligatory human pathogen. It particularly affects young adults. This bacterium mostly causes urethritis in men and cervicitis in women and affects only humans. 

Taxonomy and Classification of Neisseria gonorrhoeae

Table 1: Classification of Neisseria gonorrhoeae

Morphology and Microscopy of Neisseria gonorrhoeae

N. gonorrhoeae are oval shaped cocci which are 0.6-1 um in diameter 

They appear in pairs or flattened  

It has pili on their surface.  

The organism observed in smears from purulent materials are intracellular within polymorphs and remaining are extracellular within the exudate.  

Non-sporing 

Non-capsulated 

Gram-negative diplococci flattened along the adjoining side  

Fastidious, capnophilic and susceptible to cool temperatures, drying and fatty acids 

Cultural and Growth Characteristics of Neisseria gonorrhoeae

It is a fastidious organism and requires complex media to grow like chocolate agar, thayer-martin medium etc.  

PH required is 7.2-7.6 

Requires complex media pre-warmed to 35- 37 °C  

Soluble starch added to neutralize fatty acid toxicity  

Grow best in moist atmosphere supplemented with CO2  

Produce acid from glucose, but not from other sugars 

Enriched media with antibiotics like vancomycin, colistin, nystatin etc and lysed blood are used as a selective medium.

Small grey and glistening colonies are observed after 24hrs of incubation in selective media.

It produces five types of colnies i.e. T1, T2, T3, T4, and T5.

Type 1 and Type 2 produce small brown colonies and possess pili.

Types 3 and 4 produces large granular, nonpigmented and non-piliated colonies.

Biochemical and Identification Tests of Neisseria gonorrhoeae

N. gonorrhoeae is oxidase positive, catalase positive, ferment only glucose with acid production, and do not ferment any other carbohydrates.

Virulence Factors and Pathogenesis of Neisseria gonorrhoeae

The determinants of pathogenicity are capsule, pili, outer membrane proteins such as Por protein, Opa protein, Rmp proteins, cell wall LOS (endotoxin) and the peptidoglycan.

Antiphagocytic, capsule-like negative surface charge

Only fimbriated (piliated) cells (formerly known as colony types T1 & T2) are virulent

Outer membrane proteins (formerly Proteins I, II, & III):

Por (porin protein) prevents phagolysosome fusion following phagocytosis, thereby promoting intracellular survival

Opa (opacity protein) mediates firm attachment to epithelial cells and subsequent invasion into cells

Rmp (reduction-modifiable protein) protects other surface antigens from bactericidal antibodies (Por protein, LOS)

Acquisition of iron is mediated through Tbp 1 and Tbp 2 (transferrin-binding proteins), Lbp (lactoferrin binding protein) & Hbp (hemoglobin-binding protein)

Lipooligosaccharide (LOS) (Lipid A plus core polysaccharide but no O-somatic antigen

polysaccharide side chain) has endotoxin activity

IgA protease – destroys IgA

Acquisition of antibiotic resistance: Plasmid-encoded beta-lactamase production Chromosomally mediated changes in cellular permeability inhibit entry of penicillin, tetracycline, erythromycin, aminoglycosides

Pathogenesis            

N. gonorrhoeae is responsible for causing Gonorrhea, which is a sexually transmitted disease. At first, N. gonorrhoeae attaches to mucosal cells or mucosal surfaces of urethra via pili and other surface proteins.

Induces production of inflammatory cytokines by epithelial cells.

Evades host immune system by changing surface proteins

Often asymptomatic infection

Pili, outer membrane proteins, lipopolysaccharides

Binding to epithelial surfaces

Passage through epithelium

Interaction with phagocytes

Permeability penetration of antibiotics is controlled by outer membrane Porin- P1 and Por

Requires

Carbon dioxide

Sulfur in form of cysteine

Iron

The incubation period ranges from 2 to 8 days.

Epidemiology and Transmission of Neisseria gonorrhoeae

Almost 3 million new cases of Gonococcal disease are reported each year, mostly asymptomatic (90% in women and 40% in men). Most of them are undiagnosed, which is the main reason for the spread of the disease. Unmarried, 20-24 age groups of people are often infected. N. gonorrhea is usually transmitted through sexual contact, mother to infants during birth, and rarely from inanimate objects such as soiled towels etc. Asymptomatic carriage is major reservoir.

Clinical Manifestations of Neisseria gonorrhoeae

Most infections among men are acute and symptomatic with purulent discharge and dysuria, known for painful urination, after 2-5 days incubation period. Male host seeks treatment early preventing serious sequelae, but not soon enough to prevent transmission to other sex partners. The two bacterial agents primarily responsible for urethritis among men are N. gonorrhoeae and Chlamydia trachomatis.

As for women, they often have asymptomatic or have atypical indications (subtle, unrecognized S/S); often untreated until PID complications develop. Pelvic inflammatory disease (PID) may also be asymptomatic, but difficult diagnosis accounts for many false negatives. It can cause scarring of fallopian tubes leading to infertility or ectopic pregnancy. Gonococcal vulvovaginitis is a rare form of gonorrhea which occurs in young girls (mostly prepubertal girls).

Anorectal gonorrhea is found in homosexual men and women.

Laboratory Diagnosis of Neisseria gonorrhoeae

Specimens: Urethral and cervical discharge of acute stage, mid-stream urine 

Microscopy

Gram-negative diplococci, but in women, due to the presence of normal flora, most gram stains are gram positive.

For the rapid diagnosis of the N. gonorrhoeae, direct immunofluorescence using anti- N. gonorrhea monoclonal antibody and hybridization techniques are used.

Culture

N. gonorrhoeae is a fastidious organism. It cannot tolerate temperature changes and is intolerant of drying. Chocolate agar and modified Thayer-Martin medium are used as a selective medium for its growth. It requires high amount of CO2 for growth. Colonies appear after 24-48 hrs. of incubation. In cases of suspected sexual abuse, culture is the only accepted test for legal purposes.

Biochemical test

It is an oxidase- positive and ferments glucose with acid only.

Serology

Serological tests are mostly done for identifying asymptomatic infections in females and in complicated gonorrheal infections, mostly, when the bacteria can’t be cultured. Crude Antigen tests and Purified Antigen Tests are commonly used rapid tests. The most common test is the Gonococcal Complement Fixation Test (GCFT). It uses crude extracts of bacterium. Purified Antigen tests are the newer methods which use modern techniques: RIA (Radioimmunoassay) and ELISA (Enzyme-Linked Immunosorbent Assay).

Treatments of Neisseria gonorrhoeae

Antibiotics are mainly used for the treatment of gonorrhea in adults. The Centers for

Disease Control and Prevention recommend the antibiotic ceftriaxone for the emerging strains     of drug-resistant N. gonorrhoeae. Even after the uptake of antibiotic, it can still be transmitted for upto seven days. Therefore, CDC recommends getting tested for gonorrhoeae three months after treatment. As for the Patients with PID, combination of antibiotics (ceftriaxone and tetracycline) is used.

Prevention and Control of Neisseria gonorrhoeae              

Vaccination plays no role in prophylaxis because of antigenic variation in pilin proteins and phase variation. Tracing of contacts, health education and other general measures can be used to control gonorrhoeae. Using condoms as a barrier also can greatly reduce the rate of transmission.

References

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