Neisseria meningitidis is a gram (positive/negative) organism, and as such stains pink on gram staining.
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A 21-year-old female is brought to the emergency department by EMS after being found unresponsive in her apartment. An accompanying friend recalls the patient was at home sick for several days. The patient is unable to provide any medical history. Temperature is 38.9°C (102°F), pulse is 130/min, respirations are 22/min, blood pressure is 76/52 mmHg, and oxygen saturation saturation is 93% on room air. Physical examination is notable for a diffuse purpuric rash and cool, clammy skin. The patient’s IV, which was established en route, begins to bleed spontaneously. She is aggressively resuscitated with IV fluids, antibiotics, and peripheral vasopressors without improvement in her clinical status. Initial laboratory findings are demonstrated below:
Which of the following organisms is most likely implicated in this patient’s presentation?
Neisseria meningitidis, also called N. meningitidis or just meningococcus, is a gram-negative round bacterium that causes meningitis in humans, as well as life-threatening conditions like sepsis and disseminated intravascular coagulation.
Now, N. meningitidis has a thin peptidoglycan layer, so it doesn’t retain the crystal violet dye during Gram staining.
Instead, like any other Gram-negative bacteria, it stains pink with safranin dye.
N. meningitidis 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. meningitidis grows on a special chocolate medium called Thayer-Martin agar, which mainly consists of sheep’s 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 gonorrhoeae, also share these properties.
So the maltose fermentation test is done to differentiate the two.
To check for this, a pure sample from the culture is transferred to a sterile tube containing a mix of phenol red and maltose, which is then incubated at 36 degrees Celsius for 24 hours.
N. meningitidis causes acidic fermentation of maltose, and the resulting byproducts make the solution go yellow.
With N. gonorrhoeae, the solution stays red.
First, N. meningitidis is encapsulated - meaning it’s covered by a polysaccharide layer called a capsule.
The capsule has pili, which are hair-like extensions that help the bacteria attach to host cells.
Additionally, N. meningitidis produces toxins - and the most important one is IgA protease, a toxic protein that this bacterium uses to destroy Immunoglobulin A – IgA.
IgA is an immune system protein found in the nasopharyngeal mucosa secretions that normally osponizes invading bacteria - meaning it tags them so 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 meningitidis bacteria are still opsonized, and they get attacked by the neutrophils.
Within a neutrophil, N meningitidis gets wrapped in a phagosome, which is like a bubble inside which reactive oxygen species, such as H2O2, are released to kill it.
However, N. meningitidis releases catalase, which breaks down H2O2. Unfortunately, this translates as a win for N. meningitidis, which now takes over the neutrophil and uses its energetic resources to multiply.
The neutrophil eventually becomes too full, bursting open, and releasing N. meningitidis in the bloodstream, what’s known as meningococcemia.
Inside the bloodstream, N. meningitidis uses another toxin called factor H binding protein, which disables factor H, a protein involved in the alternate complement pathway, which plays a role in anti-bacterial immunity.
This allows N. meningitidis to spread, multiply and produce toxins in the bloodstream, causing destruction of the capillary endothelial cells, which result into leaky capillaries.
N. meningitidis also has a cell wall antigen called Lipooligosaccharide, or LOS, which can 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. Yikes!