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A 22-year-old female comes to the emergency department because of fever, headache and watery diarrhea for 12 hours. She says her stomach has been hurting since last night, and that she noticed a small amount of blood in her most recent bowel movement. She states she went on a picnic with her boyfriend 2 days ago. They ate sandwiches, chips, and consumed soft drinks. A stool sample is obtained and cultured using MacConkey agar. The colonies show non-lactose fermenting, non-hydrogen sulfide-producing bacteria. Which of the following organisms is the most likely to cause such clinical symptoms?
Content Reviewers:Viviana Popa, MD
Shigella is a Gram-negative bacterium that belongs to the Enterobacteriaceae family.
There are 4 species of Shigella:
S. dysenteriae, S. flexneri; S. boydii; and S. sonnei, and each has its own serotypes.
And shigellosis can progress to dysentery, which is when the infection causes inflammation of the colon, resulting in severe abdominal pain and diarrhea.
Now, Shigella is a gram-negative, rod shaped bacterium, meaning it looks like a little red or pink stick on a gram stain.
And it’s a facultative anaerobe, so it can survive with or without oxygen in the environment.
It has no flagellum, making it nonmotile; and it doesn’t form spores.
It’s also a non-lactose fermenter, so it doesn’t ferment lactose; and it’s urease and oxidase-negative, meaning it doesn’t produce these enzymes.
On this medium, Shigella mostly forms white, non-lactose fermenting, non-hydrogen sulfide-producing colonies
There, it targets the epithelial layer of the mucosal lining where it infects colonic enterocytes and microfold cells, or M-cells.
MALTs are a type of mucosal immune tissue that extends into the submucosa, and contains plenty of immune cells like macrophages.
Now, when a macrophage dies, it releases a variety of cytokines, including IL-1β, which activates an intense inflammatory process that recruits additional immune cells to wage war at the site of infection.
And this results in the death of epithelial cells, which damages the colonic mucosa, resulting in ulcerations and abscesses.
All the damage and migration of immune cells, particularly polymorphonuclear leukocytes, through the epithelium disrupts the cellular junctions between neighboring epithelial cells, allowing Shigella from the intestinal lumen to enter enterocytes through the lateral sides of the cell.
And actually, that’s not the only way Shigella can infect enterocytes after the initial infection:
So that means Shigella is slowly engulfed by the cell membrane, forming a membrane bound compartment that eventually pinches off from the cell membrane and ends up inside the cell, where it’s called a phagosome.
In the cytoplasm, effector proteins also induce Shigella’s actin-based motility.
This starts by recruiting the host cell’s small actin filaments to one end of the bacteria.
And as more and more actin filaments get recruited and polymerize behind the bacteria’s end pole, that propels the bacteria forward, like a rocket.
That helps Shigella “blast” through the lateral sides of both the host enterocyte and, after, the neighboring enterocyte, further spreading the infection.
Finally, one particular species of Shigella, S. dysenteriae serotype 1, also produces Shiga toxin.
Shiga toxin, similar to the shiga-like toxin producing pathotype of E. coli, is an AB toxin, so it has two main subunits, A and B, that are joined by a disulfide bond.
Each subunit plays a specific role in the invasion and destruction of a host cell.
The B subunit helps bind the toxin to the host’s cell membrane, where the toxin is ultimately engulfed into a phagosome.
Within the host’s cell cytoplasm, the inside of the phagosome becomes more acidic, and as a consequence, the disulfide bond holding the two subunits together becomes weak and eventually break, separating the subunits.
At this point, the A subunit can then diffuses through the phagosome membrane into the cytoplasm, where it targets the ribosomes.
In eukaryotic cells, ribosomes are made of two main subunits; the larger of the two is the 60S subunit, and it contains a 28S rRNA protein that’s important for the initiation of polypeptide synthesis.