AssessmentsBacillus anthracis (Anthrax)
Bacillus anthracis (Anthrax)
is a disease contracted from a certain gram positive bacillus' bacterial spores that causes fever, pulmonary hemorrhage, mediastinitis, and death if untreated.
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 44-year-old man comes to the emergency department because of dry cough, severe chest pain, and shortness of breath for the past 2 days. He states that he is the manager of a cattle farm, and is “never sick.” He wishes to get back to work as soon as possible, and his medical history is noncontributory. Blood cultures show the presence of a gram-positive rod. Chest X-ray shows mediastinal fluid accumulation and pulmonary edema. Which of the following is the mechanism of action of the toxin that is most likely producing the patient’s pulmonary edema?
Content Reviewers:Viviana Popa, MD
Contributors:Victoria Cumberbatch, Evan Debevec-McKenney, Jake Ryan, Sean Watts, Robyn Hughes, MScBMC
With Bacillus anthracis, bacillus means little rod and anthracis means coal.
So Bacillus anthracis is a rod-shaped bacteria that causes a disease called anthrax, that’s associated with characteristic black skin lesions.
Not a good reputation!
Ok, now B. Anthracis has a thick peptidoglycan cell wall, which takes in purple dye when Gram stained - so this is a gram-positive bacteria.
Also, it is a non-motile bacteria and a facultative anaerobe, meaning it can survive with or without oxygen.
B. Anthracis is also a non beta-hemolytic bacteria, because when cultivated on a medium called blood agar, B. Anthracis colonies don’t cause beta-hemolysis, where hemolysis, or breakdown of the red blood cells that surround the colonies makes the blood agar change color from red to transparent yellow.
Finally, Bacillus Anthracis is a spore-forming bacteria, so it can undergo endosporulation when it feels threatened by the environment, like when the temperature becomes too high or too low, in case of extreme dryness, or when there’s harmful radiation around.
Endosporulation means that the bacteria starts by replicating its DNA, and then it forms a wall inside the cell, isolating the big portion of the cell, let’s call it the mother cell, from the small portion of the cell.
Next, the plasma membrane of the cell surrounds the newly formed small portion and then pinches it off, forming a separate body known as a forespore.
Next, the forespore gets completely engulfed by the mother cell, something like a cell within a cell.
Finally, inside the dying mother cell, the forespore loses water and accumulates calcium, and at the same time gets wrapped in a super tough cortex from the dying mother cell.
At this point, the endospore is able to resist heat, due to the presence of dipicolinic acid found in the core of the Bacillus anthracis spore, harsh chemicals, digestive enzymes, and even antibiotics.
Finally, as the mother cell dies off, the endospore is released outside.
Surprisingly, an endospore can last over a thousand years out, waiting for favorable conditions to come, and then germinate into the bacterial, or vegetative form, which can then grow, divide and infect organisms, causing anthrax.
In humans, anthrax can infect the skin, the lungs, or the gastrointestinal tract.
In all cases, B anthracis enters the body in the endospore form, which gets phagocytosed or eaten up by resident macrophages.
For example, when the bacteria reach the alveoli, which are the tiny air-filled sacs where gas exchange occurs in the lungs, they are eaten up by lung macrophages and transported via lymphatic vessels to the nearby mediastinal lymph nodes.
A similar process occurs in both the skin and GI tract.
Inside the macrophage, the spore germinates, releasing the active form of the bacteria that then exits the cell via cytolysis or rupture of the cell membrane.
Basically, the cell bursts, releasing the bacteria into the surrounding tissues.
Now, in terms of pathogenesis, first the active form of the bacteria produces a poly-D-glutamic acid capsule that has anti-phagocytic properties, so once it is released from the macrophage it cannot be ingested by another macrophage again.
Next, B. anthracis secretes an anthrax toxin, which is composed of three proteins: protective antigen, lethal factor, and edema factor.
The protein called protective antigen gets secreted from the bacteria and then binds to the surrounding immune cells via a cell surface protein called either ANTXR1 or tumor endothelial marker 8.
It turns out that protective antigen gets its name because if a person has antibodies to this protein they are considered immune to B. Anthracis.
After binding, protective antigen forms a channel in the immune cell membrane that allows for two additional proteins called lethal factor and edema factor to enter the intracellular space.
Lethal factor is a zinc metalloprotease, which is a protein that utilizes zinc as a cofactor to cleave mitogen-activated protein kinases 1 and 2.
These enzymes help cells make NADPH, which is an important cofactor in other biochemical pathways that allow cells to generate energy in the form of ATP.
So when lethal factor cleaves these enzymes, cells can't generate ATP anymore, and eventually die through apoptosis or programmed cell death.
Edema factor gets its name from the edema it creates surrounding the black eschar.