Neisseria gonorrhoeae

Definitions & Key takeaways

Neisseria gonorrhoeae is a gram-negative diplococcus, non-spore-forming, both oxidase and catalase-positive bacteria, which is known to cause a sexually transmitted infection (STI) called gonorrhea.

Gonorrhea manifests as urethritis in males and vaginitis and cervicitis in females, and if left untreated, it can progress to gonococcemia, and cause complications like gonococcal sepsis, septic arthritis, and endocarditis. Gonorrhea is diagnosed through a laboratory test of a vaginal or urethral swab, and is treated with antibiotics.

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Neisseria gonorrhoeae, also known as N. gonorrhoeae to its friends, is a gram-negative oval bacterium that infects humans, causing a number of infections including gonorrhea.
The word Neisseria came from Neisser Albert, a German physician who discovered it, while gonorrhea is from the Greek words “gonos” which means "seed", and “rhoe” which means "flow", meaning "flow of seed", an illustration referring to the penile purulent discharge, which was mistakenly thought to be semen in infected males.
Now, a little bit of microbe anatomy and physiology. N.
gonorrhoeae is a gram-negative bacterium, because its cell wall has a thin peptidoglycan layer and so it doesn’t retain purple dye used during Gram staining.
Instead, like any other Gram-negative bacteria, N. gonorrhoeae stains pink with safranin dye.
N. gonorrhoeae typically live in pairs called diplococci, stacked side to side, so the pair looks like a coffee bean.
They are also non-motile, non-spore forming, and obligate aerobes, which means that they absolutely need oxygen to grow.
Finally, they’re catalase and oxidase positive - which means they produce both these enzymes. N.
gonorrhoeae grows on a special chocolate medium called Thayer-Martin agar, which mainly consists of sheep blood... err, yum?
Some antimicrobials, like vancomycin and nystatin are usually added to the Thayer-Martin agar, to inhibit the possible growth of undesired bacteria or fungi, and maximize the growth of Neisseria species.
However, other Neisseria species, like N. meningitidis, have the same properties.
So the maltose fermentation test is done to differentiate the two. The gist of it is that N.
gonorrhoeae can’t ferment maltose, whereas N. meningitidis can.
To check for this, a pure sample from the culture of the suspected bacteria, is transferred to a sterile tube containing phenol red-maltose broth, which is then incubated at 36 degree Celsius for 24 hours.
Since N. gonorrhoeae can’t ferment maltose, the solution stays red, whereas with N.
meningitidis, fermentation byproducts make the solution go yellow. Now, unlike its sister Neisseria meningitidis, Neisseria gonorrhoeae is not an encapsulated bacteria, so it doesn’t have a polysaccharide capsule.
But this bacteria has a ton of other virulence factors, which it uses to attack and destroy host cells, and also to evade the immune system.
First, N. gonorrhoeae has pili, these little thread-like extensions radiating from the bacterial surface.
The pili help N. gonorrhoeae attach to a host’s mucosa surface.
Also, they help bacteria get physically connected with each other, making what’s known as a conjugation pilus, which is a hollow tiny rod, through which bacteria can swap genetic information back and forth - including antibiotic resistance genes.
Interestingly, N. gonorrhoeae pili are made of antigenic proteins which can vary with every infection – what’s known as phase variation.
Ok, so normally, when a certain bacteria causes an infection, the immune system keeps memory of the bacterial antigens configuration.
So if the same bacteria infects again, the immune system remembers it and quickly makes specific antibodies against it. However, since N.
gonorrhoeae changes the antigens on its pili each time it infects a host, the immune system can’t produce a quick specific immune response.
Phase variation is also the reason why there’s no effective vaccine against N. gonorrhoeae.
Pili aside, other virulence factors of N. gonorrhoeae include toxins.
The very important one is IgA protease, a toxic protein that this bacterium uses to destroy Immunoglobulin A – IgA. IgA is an immune system protein that’s normally found in the mucosa secretions, like those produced by the vagina or the cervix.
IgA helps with bacteria opsonization - meaning it tags the bacteria so that neutrophils can recognize and destroy them. So IgA protease neutralizes the first line of mucosal defense!
However, not all IgA molecules get neutralized, so some N. gonorrhoeae bacteria are still opsonized, and end up getting attacked by neutrophils.
Inside the neutrophil, N. gonorrhoeae is wrapped in a phagosome, a bubble inside which reactive oxygen species, such as H2O2, are released to kill it.
However, N. gonorrhoeae releases catalase, which breaks down H2O2.
Unfortunately, this translates as a win for N. gonorrhoeae, which now takes over the neutrophil and uses its energetic resources to multiply.
The neutrophil eventually becomes too full, bursting open, and letting out a lot of bacteria in the bloodstream, which is known as gonococcemia.
Inside the blood, N. gonorrhoeae can use other virulence factors.
First, there’s a cell wall antigen called Lipooligosaccharide, or LOS, which is known for its ability to trigger a widespread immune reaction that results in sepsis - meaning blood vessels dilate, so blood pressure drops, and vital organs don’t get enough blood.
And one final virulence factor of N. gonorrhoeae is its ability to do sialylation, a process by which N.
gonorrhoeae wraps its LOS cell wall with sialic acid, the same molecule initially found in the host’s cells. This helps the bacteria to hide its LOS antigen, making itself anonymous to the host’s defense system - like camouflage.
As if that wasn’t enough, N. gonorrhoeae can spread from the bloodstream to other parts of the body, like the joints or the heart.
Most frequently though, N. gonorrhoeae causes gonorrhoea, which is a sexually transmitted infection.
In males, gonorrhoea manifests as urethritis, or inflammation of the urethra, but it can also affect the prostate, causing prostatitis, or the epididymis, causing epididymitis.
In females, N. gonorrhoeae can also cause urethritis, but most frequently it causes vaginitis and cervicitis - so inflammation of the vagina and cervix, respectively.
Through the cervix, N. gonorrhoeae can spread to the uterus, the fallopian tubes and sometimes even the ovaries, causing causing pelvic inflammatory disease, or PID.
Finally, PID can cause a complication called Fitz-Hugh-Curtis syndrome, which occurs when the inflammation spreads to the peritoneum, and, from there, to Glisson's capsule, which surrounds the liver.
This results in “violin string” adhesions, or thin strings of scar tissue that attach the liver to the peritoneum. If N.
gonorrhoeae infects pregnant women, it can spread to the baby during vaginal delivery, and results in “early neonatal conjunctivitis” – so a type of conjunctivitis that affects the newborn 2 to 5 days after birth.
N. gonorrhoeae can also cause some rare, but serious infections, often as a consequence of gonococcemia.
When the infection spreads to the joints, it may cause gonococcal arthritis, which is more common in sexually active adolescents.
If it spreads to the heart, it may affect the heart valves, causing endocarditis. The first symptoms of a Neisseria gonorrhoeae infection are related to the genital infection.
in men, there can be burning sensation when urinating, as well as clear urethral discharge, which can become purulent and bloody.
In women, there’s usually thick, white, purulent vaginal or urethral discharge, which can also turn bloody sometimes. If the infection progresses to PID, there may be lower abdominal pain and fever.
Alternatively, with neonatal conjunctivitis, there can be swollen eyelids with mucus and pus discharges from the eye. In gonococcal arthritis there is multiple joint inflammation which results in painful swelling of the wrists, ankles, and elbows.
With gonococcal endocarditis, there may be fever, chills, sweating and malaise. Diagnosis is usually done with a vaginal or urethral swab, which is then smeared on a slide for biochemical tests and gram staining - which reveals pink coffee-bean shaped bacteria within neutrophils.
Growing the bacteria on Thayer-Martin agar is required for confirmation, but nucleic acid amplification testing, or NAAT, can also be done - and this consists of identifying the bacterial genetic material.
Treatment for N. gonorrhoeae infections is with third generation cephalosporins, typically ceftriaxone.
However, it has been found that gonococcal infections are frequently associated with a Chlamydia trachomatis coinfecton.
So, usually azithromycin or doxycycline are given along with ceftriaxone, to also cover chlamydia. Finally, since gonorrhoea is a sexually transmitted infection, it can be prevented by using condoms during sex.
Alright, as a quick recap, Neisseria gonorrhoeae, is a gram-negative diplococci that grows best on Thayer-Martin agar. It’s non-motile, non-spore forming, oxidase positive, and catalase positive, but maltose negative.
It lacks a capsule, but has other virulence factors like pili, and proteins like pilC, Opa, and IgA protease. Most frequently, N gonorrhoeae causes gonorrhea, which commonly manifests as urethritis in males and vaginitis and cervicitis in females.
Left untreated, N. gonorrhoeae infections can progress to gonococcemia, and cause complications like gonococcal sepsis, septic arthritis, and endocarditis.
Treatment is with ceftriaxone, and azithromycin or doxycycline are also given to cover a possible chlamydia coinfection.