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Neisseria meningitidis

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Neisseria meningitidis

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USMLE® Step 1 style questions USMLE

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A 20-year-old man, currently a university student, is brought to the emergency department after being found unconscious on the floor in a dorm room. Physical examination shows purple-rose spots on the neck, abdomen, and lower legs. Temperature is 39.5 °C (103.1 °F ), pulse is 120/min, respirations are 18/min, and blood pressure is 84/51 mmHg. The gram stain from serum testing is shown below. Which of the following characteristics is true regarding the causative pathogen of this patient’s condition?  


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Content Reviewers:

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.

The gist of it is that N. meningitidis can ferment maltose, whereas N. gonorrhoeae cannot.

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.

Now, N. meningitidis has a number of virulence factors, that are like assault weaponry that help it attack and destroy the host cells, and evade the immune system.

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.

Underneath the capsule, there’s the outer cell membrane, which has two opacity proteins, called Opa and Opc, that also help N. meningitidis 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!

Summary

Neisseria meningitidis also known as meningococcus, is a gram-negative diplococcus, non-spore-forming, both oxidase and catalase positive, which is commonly known to cause meningitis. Meningitis is an infection of the membranes called meninges that surrounds the brain and spinal cord.

When meningococcal bacteria enters the bloodstream, it's referred to as meningococcemia. Meningitis most commonly results from meningococcemia and is associated with outbreaks, especially in unvaccinated people living in crowded settings, like dormitories, military barracks, and schools.

Symptoms of meningococcal meningitis include fever, headache, stiff neck, and a rash. Other symptoms may include nausea, vomiting, sensitivity to light, and altered mental status. Meningitis can progress rapidly and can be fatal if not treated promptly with antibiotics.