Bacillus anthracis (Anthrax)

Definitions & Key takeaways

Bacillus anthracis is an encapsulated, spore-forming, gram-positive bacteria bacterium that's known to cause anthrax. Anthrax can cause severe pulmonary, gastrointestinal, or cutaneous illnesses in humans. Anthrax can be transmitted via ingestion, inhalation, and skin invasion by the bacteria or its spores, often via direct interaction with infected animals.

It is more seen in agricultural regions where livestock are infected with the bacteria. Depending on the affected organs, it can present with a black necrotic skin lesion; fever, respiratory distress, abdominal pain, septic shock, and death if bloodstream infection occurs.

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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.
Throughout history, Bacillus anthracis, or B. anthracis for short, has caused a number of plagues in Europe, and it’s also been used as biological warfare.
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. It contains ADP ribosyltransferase, which converts adenosine triphosphate to cyclic adenosine monophosphate, or cAMP.
cAMP activates the protein kinase A signaling pathway and thus leads to activation or inactivation of many cellular functions.
Importantly, activation of this pathway perturbs the cell's ability to secrete cytokines, which are signal molecules that call for white blood cell reinforcements to neutralize the bacteria.
So the bacteria multiply and destroy immune cells in the lymph nodes, preventing an appropriate immune system response, causing surrounding necrosis and eventually bleeding.
Access to the bloodstream now allows the bacteria to travel to multiple organs through the bloodstream causing even more necrosis, leading to multi-organ failure, septic shock, and death.
Clinically, anthrax has three forms. Skin, or cutaneous anthrax is the most common form of the disease and results when endospores come in contact with an open break in human skin, usually via animal hair or wool.
Here, the endospores also germinate locally, producing both additional spores as well as active bacteria that form painless small red bumps or papules that eventually becomes a large vesicle, or fluid filled sac that ruptures.
After rupture, the surrounding tissue begins to necrose or die, leaving behind a characteristic painless black skin lesion called an eschar.
Gastrointestinal anthrax occurs when a person ingests undercooked animal meat infected with spores. The ingested spores can infect any part of the GI tract from the mouth to the rectum, and through a similar process to that of the skin, they can cause the formation of black eschars.
Symptoms include abdominal pain, nausea and vomiting, especially vomiting blood, and diarrhea or bloody diarrhea. Respiratory anthrax, also known as woolsorter’s disease, occurs when a person inhales anthrax spores.
However, in this form of disease black eschars do not appear in the lung but instead in the surrounding mediastinal lymph nodes.
This can lead to pulmonary hemorrhage, severe mediastinal lymph node necrosis, and bacteremia, which is when the bacteria enters the bloodstream.
This results in coughing up bright red blood, high fevers, low blood pressure, and a fast heart rate. So unfortunately, this form of anthrax is associated with the highest mortality rate.
Diagnosing anthrax can be difficult because of its rarity and the fact that most hospitals are not equipped with the proper diagnostic tools.
The tools that are used to diagnose anthrax include a polymerase chain reaction assay that directly detects B. anthracis DNA, immunohistochemical staining of tissues, which identifies B.
anthracis antigens in tissues, and an anti-protective antigen immunoglobulin assay, which identifies antibodies against protective antigen.
Other clues to diagnosis include a widened mediastinum on chest x ray due to progressive mediastinal lymph node necrosis.
Treatment of anthrax involves intravenous antimicrobial combination therapy, anthrax antitoxin, and supportive care. First line antimicrobial agents include ciprofloxacin along with either clindamycin or linezolid.
Finally, Raxibacumab and obiltoxaximab are two monoclonal antibodies that directly inhibit the protective antigen and should be administered to anyone confirmed of having fulminant systemic anthrax.
##Summary All right, as a quick recap: Bacillus Anthracis is a rod-shaped gram positive spore forming organism that causes a disease called anthrax.
The spore form of B. anthracis allows the organism to survive extreme environmental conditions, and it’s also the infectious form of the bacterium.
B anthracis causes respiratory, gastrointestinal, or cutaneous disease, using virulence factors like protective antigen, lethal factor, and edema factor.
All three forms can progress to fulminant disseminated anthrax. Confirming the diagnosis is done with a positive polymerase chain reaction, immunohistochemical staining, or anti-protective antigen immunoglobulin assay.
Treatment of anthrax involves intravenous