Amoeba: The Dangers Around Us

Amoebae

Beads of sweat drip down your forehead as the summer heat weighs down on your body. Wondering what to do, you remember that there is a lake nearby and decide to cool down there. Soon, your disgust with the weather dissipates as you dive into the water. What you don’t realize, however, is that you may have put yourself at risk for one of the deadliest conditions known, a condition that begins with an amoeba.

Similar to bacteria, amoeba are single-celled microorganisms. However, unlike bacteria, amoebas are eukaryotes, meaning their DNA is stored within the nucleus. Amoebas have numerous unique qualities they rely upon for survival. For example, to move around, an amoeba can create small bulges out of its body to push and drag themselves along. These temporary extremities are called pseudopodia, which is Latin for “false feet.” Pseudopodia are also used to engulf prey such as bacteria, algae and fungi. Amoeba can be found throughout the world, but it is most commonly seen in soil, freshwater, and other wet habitats. Generally speaking, these organisms are harmless to humans and are rather essential to the function of our planet by being key players in microbial communities, nutrient cycling, and energy flow.

Recently, scientists have decided to take a closer look at the interesting relationship amoeba can have with bacteria. Considering that the primary relationship between amoeba and bacteria is that of predator and prey, researchers believe that an amoeba has the potential to act as a repository of information regarding how cells evolve within these relationships. This is important as amoeba cells are generally similar to human body cells due to their eukaryotic nature, although an amoeba tends to be much cooler than a mammalian body. A potential use of amoeba comes from Amoeba-Resistant Bacteria (ARBs), which are bacteria that have learned to adapt and resist amoeba. Amoeba and bacteria relationships have also been studied in regard to horizontal gene transfer. The long history of their interactions, which dates far before humans, provides researchers with the opportunity to understand how such intense interactions could lead to certain organisms gaining genes from another organism. It has already been discovered that many ARBs have gained their resistive traits from amoebas themselves. This highlights the general impact that amoebas have on humans and our planet.

However, not all amoebas are helpful to the human cause. Certain amoebas are human pathogens, infecting humans in a similar way to bacteria and causing damage. There are a wide number of different pathogenic amoebas, all differing in their routes of infection and symptoms. For example, Entamoeba histolytica is an amoeba that is causing a global health concern through the disease amebiasis. Entamoeba histolytica causes diarrhea, stomach pain, and the deaths of about 100,000 people per year, most commonly those who live in tropical areas under poor sanitary conditions. It thus becomes clear that amoeba, while generally harmless and a great focus for research, can, at times, be an incredibly harmful agent. Still, one of these pathogenic amoeba stands out amongst the rest, spurring immense fear among the general population.

Naegleria Fowleri

Recently, through social media platforms, many have become aware that a strange yet dangerous condition exists that causes your brain to be eaten, but what exactly is it? The condition is called Primary Amebic Meningoencephalitis (PAM), which attacks one’s central nervous system, consisting of the brain and spinal cord. It is caused by an amoeba called N. fowleri, which, similar to those described above, is a microscopic species. The amoeba stems from the genus Naegleria, a group of free-living amoebae flagellates, which are amoebas that generally live in the outside environment but can also be found in animal species. Of the thirty species within this genus that have been identified, only N. fowleri directly impacts human lives. The amoeba typically thrives in warmer climates due to its thermophilic nature. Thermophiles are organisms that thrive at higher temperatures, generally between 41 to 122 degrees Celsius. Hence, humans are more likely to interact with it when the weather gets warmer and they seek water sources to cool off. Hence, as expected, the region in the United States with the highest infection rate was the South, particularly Florida and Texas, likely due to their warmer climates.

In order to survive, N. fowleri transforms between three different stages: the cyst, trophozoite and flagella stages. It is in the trophozoite stage that the amoeba poses a threat to humans. A trophozoite is about 10-35 µm long and is the state that the amoeba will stay in if food is readily available. They will transform into a smaller, flagellated stage (10-16 µm) due to unfavorable environmental stages, such as food shortages. The trophozoite can also transform into a cyst stage (7-15 µm) in difficult environmental states, such as cold weather, to survive. However, it is only in the trophozoite stage when N. fowleri can harm our central nervous system, since that is the only stage it hunts for food. Doctors and scientists have only found amoebas that are in their trophozoite state in human cerebrospinal fluid and tissue.

N.Fowleri Infection

How does a trophozoite enter the human body? When a human interacts with N.fowleri, it must infect them by entering through the nasal tissue to be harmful. Hence, if a human were to jump into a lake infested with N. fowleri, if they keep their head above water or even drink the water, they would be fine. This is because humans have a number of natural antibodies that prevent the amoeba from harming them. However, when it enters through the nose, it can attach to the nasal mucosa, allowing it to transport throughout one’s olfactory nerves and bulbs. Mucosa fills the inside of our nose and is the first immune defense for all invaders that enter through the nasal cavity. It is a slime-like substance that is used to kill or stun invaders. The mucosa can notify immune cells that an invader has entered the body. Scientists have speculated that the reason our immune system doesn’t immediately respond and kill the amoeba is that certain eukaryotic cells have complement-regulatory proteins that prevent them from being affected by lysis. Lysis is the process of killing a cell by destroying its outer cell membrane. In vitro studies have confirmed that N.fowleri expresses a particular complement-regulatory protein that prevents the formation of a membrane attack complex. This protein is thus able to prevent complement-activated lysis. Scientists have equated this process to the amoeba creating a false friendship with our body allowing it to bypass these responses.

If the amoeba makes it through the mucosa and up the nose, it finally finds something that captivates them. Our nose has olfactory cells that can pick up molecules that come through the nose and send information to our olfactory bulbs in our brains, which control our sense of smell. In order to reach the olfactory bulb, our nerve cells use molecules, called neurotransmitters, to help channel information. One of these neurotransmitters is acetylcholine. To the misfortune of humans, N. fowleri contains receptors that recognize acetylcholine. Acetylcholine has long been known to be attractive to eukaryotic cells, which is generally helpful to humans as it can guide our immune cells to sites of infection quickly. The immune cells have G-protein-coupled receptors (GPCRs) on their surface where the acetylcholine binds to and helps direct the cell to the direction the acetylcholine is headed. Similar to these binding areas held on our own cells, scientists have recently discovered N. fowleri has a strong attractive force that allows the acetylcholine to bind to the GPCRs on the amoeba’s body.

Now attached to the acetylcholine, the amoeba are able to penetrate our olfactory epithelium, the tissue in our nasal cavity that houses our olfactory nerves, and move to the brain. As it enters our central nervous system, our body responds to the foreign substance by sending large numbers of neutrophils to the amoeba. Neutrophils are white blood cells, that act as our body’s first line of defense against invaders. The neutrophils can work together to release chemicals to destroy the amoeba and even work to tear them apart. Unfortunately, these amoebas are large and come from an environment where they gained the evolutionary skills to survive harsh situations. Hence, the amoebas are able to withstand much of the damage. Although some of the amoebas may be killed by the neutrophils, they aren’t enough to handle all of the N. fowleri that enter our bodies. Scientists suggest that this is the path of least resistance for N. fowleri as it can bypass many of our body’s natural central nervous system protections and barriers. Consequently, as the acetylcholine makes its way toward our olfactory bulbs, the N. fowleri is also sent upon a direct path to our brains.
It can take between one to nine days for the amoeba to reach your brain, with an average rate of five days. Until this point, you wouldn’t notice anything, as your first symptoms occur only upon the arrival of amoebas to the brain. The amoebas have now grown tired from traveling throughout our nose and through the central nervous system, so they begin to look for food. However, due to the absence of bacteria in human brains, the amoeba begins to look towards your cells. They first release a number of attack molecules towards the cells to break them apart. The cells are now much more easily consumed by the pseudopods of the amoeba. Now in the brain, the N. fowleri transforms within the trophozoite state. It changes a transmission electron micrograph (TEM) with a central and electron-dense nucleus to the scanning electron micrograph (SEM) where the trophozoites develop “food cup” structures. These “food cups” are all around the surface of the amoeba to help them rip apart and vacuum our brain cells. Scientists have related the behavior of the amoeba to suction cups, slowly tearing apart sections of the brain. Now being fed, the amoeba begins to replicate and feast on one’s brain at a higher rate.

As a response to the loss of brain cells, the body sends many immune cells to the site of infection. This is a major concern as our immune cells generally aren’t fighters that can fight off specific targets, but rather, they create wide ranges of damage in order to deal with the infection. Generally, this is safe, but since this particular infection occurs in the brain, humans cannot afford to damage their cells in this battle. Even with the presence of many immune cells, the N. fowleri does not go down easily. The complement system on the face of N. fowleri is able to catch and disable proteins that are launched at the amoeba that are generally able to act as bombs and destroy invaders. N. fowleri is also very successful at swallowing and disabling our natural antibodies. Our body also creates a high fever, in hopes that the temperature increase would help kill or at least slow down the infection. However, due to the aforementioned thermophilic nature of N. fowleri, the amoeba can thrive in the increased temperature.

Lastly, our brain begins to pump blood into the brain to both trap the invaders but also to heal the damaged brain tissue. However, the brain can only be inflamed a minor amount before it begins to have contact with the skull, which prevents further expansion. Throughout this battle between one’s immune cells and the N. Fowleri in the brain, the human will slowly begin to experience more severe symptoms. It first begins with a headache, fever, and nausea. However, as time passes, the battle continues, causing confusion, the inability to concentrate, and hallucinations. Once the brain cannot inflame any further due to the lack of space, the brain will begin to compress and shut down its brain stem, at which point, the person is confirmed as dead. The brainstem is a structure that connects our spinal cord to the cerebellum and it is essential to send out many signals that control our subconscious body procedures, such as breathing and heart rate. Hence, it is impossible for one to live without their brain stem.

It is clear that N.fowleri is a threat to humans. Generally, patients die less than a week after the first symptoms. N. fowleri has an incredibly high fatality rate as 97% of those infected with N.fowleri have passed away. Scientists have also noted that children are more likely to be infected by PAM, with the median age of infection being 12 years old in the United States. Many argue that this is just since children tend to be in situations where they are surrounded by N.fowleri. However, it is also possible that there is an anatomical reason for this trend. Children and young adults have more porous cerebriform plates. These plates support the olfactory bulb, meaning that if they are more porous it gives the amoeba a greater chance of being able to reach the bulbs.

It is clear that N. fowleri is a threat to human life, but should one simply avoid water activities in warm climates? Thankfully, these precautions don’t necessarily have to be taken due to the rarity of this condition. Since 1937, there have only been 387 confirmed cases of PAM. Within the United States every year, there is a range of 0-8 PAM infections. Compare this to other ways people have passed away. In 2019 alone, there were about 236,000 deaths caused by drowning. For now, at least, PAM is not at the top of our medical concerns.

So on that hot summer day, feel free to bathe in your local lake, but be aware of the dangers that may lurk within the water.

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