Corynebacterium diphtheriae (Diphtheria)

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Corynebacterium diphtheriae (Diphtheria)

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Corynebacterium diphtheriae (Diphtheria)

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Corynebacterium diphtheriae forms (colored) colonies on cysteine-tellurite agar.

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A 30-year-old woman comes to the clinic because of a sore throat, cough, and tiredness. She immigrated from Indonesia two years ago and has not had to seek medical care until now. Her temperature is 38.5°C (101.3°F), pulse is 85/min, respirations are 22/min, and blood pressure is 130/80 mm Hg. Her symptoms started with a mild sore throat nine days ago and have progressed to pain when swallowing solid foods. Examination of her oropharynx shows the following grayish white lesion that bleeds slightly with scraping:
 
She also has prominent cervical lymphadenopathy, swelling of the anterior neck, and stridor. Which of the following is the most likely diagnosis?

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Corynebacterium diphtheriae or just C. diphtheriae takes its name from the Greek;. “Coryne” that means club, and “diphtheriae,” which means leather.

So to sum this up, C. diphtheriae is a club-looking bacteria that causes diphtheria, an infection with a characteristic tough leathery membrane that forms in the pharynx.

C diphtheria has four main subspecies; C. diphtheriae mitis, C. diphtheriae Intermedius, C. diphtheriae Gravis, and C. diphtheriae Belfanti.

OK, now, C. diphtheriae has a thick peptidoglycan cell wall that takes in purple dye when Gram-stained - so it’s a gram-positive bacteria.

It is aerobic, which means it requires oxygen to grow, and it doesn’t form spores.

Now, when stained with Albert’s stain, these bacteria demonstrate some unique features.

They look like green, club-shaped bacteria with metachromatic granules, which are these dark blue dots made of phosphate, located at the bacterial poles.

When many, and clustered together, these bacteria seem to be arranged in a characteristic pattern that resembles Chinese letters.

Finally, C. diphtheriae is a fastidious bacteria.

This means it can only grow on special nutrients-enriched media.

The medium commonly used to grow this bug is cysteine-tellurite blood agar on which C. diphtheriae grow into black colonies.

Alright, any of the C. diphtheriae subspecies can be either toxigenic or not, depending on whether or not they produce the diphtheria toxin, or DT for short.

DT is a cytotoxic protein, where cytotoxic means it causes damage to host cells.

In fact, all the C. diphtheriae subspecies start out as non-toxigenic, but they become toxigenic after they’re infected by a beta-bacteriophage.

This is a kind of virus that attaches to bacteria and merges its own genome with the bacteria’s.

The beta-bacteriophage genome contains tox-genes, which code for diphtheria toxin production.

Following this, C. diphtheriae can make DT, and, in turn, cause diphtheria.

Now, DT has two main subunits, A and B, joined by a disulfide bond, with each of the subunits playing a specific role in the invasion and destruction to the host's cells.

The B subunit, which is the Bigger portion of DT complex, helps Binding to the host’s cell membrane.

After attaching to the host’s cells, the whole DT complex gets slowly engulfed by the cell membrane, which invaginates to form a sac on its inner side.

The sac then separates from the actual cell membrane forming a vesicle called an endosome.

Within the host’s cell cytoplasm, the medium inside the endosome becomes more acidic, and as a consequence, the disulfide bond holding the two subunits together becomes weak and eventually break, separating the subunits.

The A subunit then diffuses through the endosome membrane into the cytoplasm, where it goes straight to the ribosomes.

Here, it interferes with cell protein synthesis.

This happens because the A subunit has an ADP-ribose group, which attaches to the elongation factor - EF2, an important ribosomal protein that joins amino acids together during protein synthesis.

This process is called EF2 ADP-ribosylation, and it results in complete deactivation of the EF2, which stops protein synthesis, leading to cell death.

Ok, now, C. diphtheriae mainly causes diphtheria in unvaccinated or immunocompromised people.

Most often, the bacteria can be transmitted from one person to another mainly by respiratory droplets, following coughing or sneezing, in which case it causes pharyngeal diphtheria, but they can also enter the body through open lesions on the skin, causing cutaneous diphtheria.

Following inhalation of infected respiratory droplets, C. diphtheriae attaches to the pharyngeal epithelial cells, where they release DT toxin.

This causes local inflammation that leads to necrosis of pharyngeal tissue, and neck swelling.

The necrotic tissue builds up over the pharynx and larynx forming a gray adherent leathery membrane, commonly referred to as a pseudomembrane.

In some cases, a portion of this pseudomembrane can detach and get lodged into the trachea or bronchi, and when it is big enough, it can block the airways completely, causing death by asphyxiation.