Leprosy has been a disease that has plagued history books. With certain famous figures, such as 12th century King Baldwin the fourth, who suffered from leprosy since the age of 6. Media has commonly depicted Baldwin as adorning a mask to cover the facial disfigurement due to the disease, but some historical evidence has pointed to him using a veil to cover the effects of the disease. Many see leprosy as this ancient disease that has been drowned out by antibiotics and other treatments. However, according to the World Health Organization around 200,000 people suffer from this disease a year. With 95% of people having a natural immunity though, leprosy rarely makes headlines. Hence, research regarding treatments and cures have fallen short. These treatments commonly kill the bacteria, but do not prevent the side effects that come from the infection. These side effects from leprosy include extreme damage to the skin, eyes, and nervous system, meaning those who suffer with leprosy do not feel the pain associated with the infection.
“Baldwin King of Jerusalem” and “Majesty and Ruin,” an artistic rendition of King Baldwin. Source
What causes Leprosy?
Leprosy is caused by the bacteria Mycobacterium leprae which infects Schwann Cells. Schwann cells are primary neurological cells found in the peripheral nervous system which help support the nervous system. M. leprae are rod shaped bacteria that have a special affinity for these Schwann cells. Equipped with special mechanisms that allow for the hijacking of Schwann cells, once these cells are overtaken by M. leprae, they become vehicles for the bacteria to move around and infect the body. M. leprae hijacks these cells by attaching to them and then changing their genetic information to benefit themselves. They are able to manipulate the cell’s genetic information to turn the cells into unspecified stem cells, losing their abilities to help the nervous system function properly.
Many therapies have been developed in order to battle leprosy, including Multi drug therapy (MDT), which is an important step in treating many bacterial diseases. Unfortunately, cures and treatments still lag when addressing leprosy. Even with hundreds of years of recorded instances of leprosy, the treatment for it usually relies on antibiotics, and other drugs to help kill the bacteria. MDT is successful at eliminating the bacteria, but usually does so too late, and the patient will still suffer from nerve damage. Hence, without understanding the mechanisms in how leprosy takes over the host cells, curing it seems further and further away. However, the paper IDO-Mediated Immune and Metabolic Dysregulation in Schwann Cells Exposed to Mycobacterium leprae, found a way that M. leprae hijacks these cells in order to take over the entire body.
M. leprae in red hanging with other cells. Source
The main reason that 95% of humans are naturally resistant to leprosy is because of their immune systems being able to find and destroy the bacteria before they are able to fully hijack the cells. However, to ensure their survival against the immune system, the bacteria will change the genetic information of these cells to create a more safe environment to flourish in. One way they accomplish this is by having the cell produce more of an enzyme called indoleamine 2,3-dioxygenase, or IDO.
IDO’s introduction page
IDO is a vital enzyme, nicknamed a double edged sword, that regulates immune system response and metabolism within the Schwann cells. IDO, in high concentrations, can affect the immune system by breaking down certain amino acids and proteins within cells, creating an immunosuppressant environment. Additionally, IDO regulates metabolism within the cells, which when cell metabolism is running correctly, allows for the cells to receive adequate energy. Regularly Schwann cells seem to utilize fermentation as a metabolic pathway to acquire energy. Fermentation is a pathway that can occur with little to no oxygen and will result in energy and lactic acid. While glycolysis is a metabolic pathway that utilizes sugars to create energy in cells . However, with too much IDO, the metabolic pathway favors altered glycolysis rather than fermentation, eventually leading to lipid droplet production.
Lipid droplets residing next to different cell organelles. Source
M. leprae takes advantage of this crucial enzyme by exploiting it and having the cell produce so much of it that it becomes immunosuppressant and the metabolism of the cell is greatly affected. In this immunosuppressant environment, it is much more difficult for the hijacked cell to be targeted by the immune system and therefore eliminated. Additionally, when M. leprae increases the amount of IDO and the metabolic pathway favors altered glycolysis, lipid droplets will be produced. These droplets provide essential nutrients and a safe haven for M. leprae, shielding it even further from the immune system. However, it seems that a high presence of IDO also decreases metabolic activity entirely due to downstream effects on other enzymes and proteins.
M. leprae in action
In order to test for these heightened levels of IDO, Rahman and colleagues took Schwann cells from patients and infected them with M. leprae. They then measured how much IDO was in each cell, by observing the number of proteins that are affected by high levels of IDO. They compared this number to the IDO amount in healthy Schwann cells.
Figure 1. In B, it shows the increased IDO expression in cells infected with M. leprae compared to healthy cells. In D it shows the lack of metabolic activity in infected cells compared to the healthy cells.
These results depict that M. leprae hijacks the Schwann cells and causes them to overproduce IDO. Which will lead to a lack of metabolic activity in the cells, and eventually to droplet formation. Which allows M. leprae to flourish and continue infecting the host without intervention from the immune system. Additionally, this figure depicts that overall IDO activity almost doubles in cells infected with M. leprae compared to healthy cells. Depicting the way that M. leprae takes over host cells and changes genetic information for its benefit.
Why does this matter?
IDO in low amounts can be greatly beneficial for cells, by regulating metabolism and ensuring a healthy environment supporting the immune system. However, when bacteria take advantage of this enzyme and overproduce it, it can eventually lead to wide-spread infection, due to the creation of a suitable environment for the bacteria to flourish in. The ability for bacteria, such as M. leprae, to hijack certain cells and mechanisms are specialized techniques developed for survival of the bacteria. Due to these specialized abilities treatments for these specific diseases can unfortunately lag. These treatments focus solely on killing the bacteria when it has already taken over host cells and caused damage to the nervous system, as they do not help prevent or counteract nerve damage. However, with this new research treatments can be developed which can target mechanisms, such as the overproduction of IDO, and hopefully prevent nerve damage. By hindering M. leprae from hijacking and manipulating the genetic information of the Schwann cells, IDO production remains at normal levels, and M. leprae can remain susceptible to the immune system. Hopefully with more research dedicated to understanding mechanisms M. leprae uses to hijack host cells, this ancient disease can truly be a product of history.
About the Author:
Elise Krone ‘27 is a junior at Mount Holyoke College. She is a biology and psychology double major, also pursuing the Culture, Health, and Science certificate. She studies Bacillus subtilis sporulation in the Camp Lab on campus. In her free time she enjoys being with her friends, crafting, and playing video games.
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