ML Bacteria and the Benefits of Leprosy

When you hear the word “leprosy”, you may think of the bacterial infection that causes skin lesions and nerve damage, and the associated social stigma. However, according to some scientists, studying the bacteria that cause Hansen’s disease could provide incredible benefits to liver research, thanks to one funky little mammal.

Hansen’s disease is an infectious disease caused by a bacterium called Mycobacterium leprae (ML). In humans, these bacteria infect Schwann cells, which provide insulation for the long axons of nerve cells. When nerve cells are damaged from an injury or infection, Schwann cells receive signals to revert to a relatively immature state, known as de-differentiation. This helps the axons regenerate and allows the peripheral nervous system to recover.

When a person contracts Hansen’s disease, the ML bacteria use this system to their benefit. They reprogram Schwann cells not just into an immature, de-differentiated state, but even further into something resembling a stem cell. This process causes damage to axons by breaking down the myelin sheath, which makes it easier for the bacteria to invade and evade the immune system.

Surprisingly, ML bacteria have the nearly the opposite effect in liver tissue of nine-banded armadillos, native to North and South America. A 2022 study from researchers at the University of Edinburgh has shown that nine-banded armadillos infected with the ML bacteria grow bigger livers that are healthy and functional in all respects. The bacteria increase the expression of genes that code for proteins associated with growth, wound-healing, and increased metabolic responses in the liver, which are very similar to genes and proteins expressed in human liver cells during fetal development and adult growth. This de-differentiation that ML causes in armadillo livers is temporary, allowing the cells to proliferate and then re-differentiate into healthy specialized liver cells. This is less damaging than the de-differentiation that ML causes in human nerve cells, where their reversion to a stem-cell like state trashes their ability to heal themselves since they cannot re-differentiate. This shows how very similar effects at the cellular level can lead to wildly different effects in different tissues and different organisms.

Now, tissue regeneration is an active area of study for a couple of reasons. In humans, we want to keep organs healthy as people age, and we want to understand how to heal damaged tissue without cells growing out of control and becoming cancerous. Scientists can revert mature cells to a more stem cell-like state in rodent models. But… those cells tend to become cancerous, which makes that method no good for healing damaged organs in humans without some serious further study.

Well, guess what armadillos infected with ML bacteria DON’T have? They don’t have liver cancer! The researchers did not find any masses, tumors, or other tissue abnormalities in any of the infected armadillos. And the ML bacteria’s little reprogramming act has little effect on genes that encourage tumor growth. This reprogramming is likely beneficial to the bacteria themselves, because by causing cell proliferation and increased liver size, the bacteria get a nicer, more nutrient-packed habitat. The bacteria also protect themselves by keeping the host healthy, so it’s in their interest to not cause any real harm to the host’s liver.

And this isn’t just, like, ok, well very lucky for armadillos I guess, because the researchers in the study think this makes armadillos a great way to study how liver tissue regenerates and apply that knowledge to humans. Liver disease causes millions of deaths around the world every year. The human liver is typically able to heal itself when needed. But that can be impaired in cases like liver failure or cirrhosis. The researchers are hopeful that using armadillos as a model of liver regeneration could help us develop tools to heal damaged livers in humans, or maybe even grow brand new livers to order when a transplant is needed.

Which is a pretty unexpected upside to one of the most hated diseases in human history interacting with one of my favorite little animals. I’d like to think that it could even help break down some stigma against people living with Hansen’s. Sometimes, nature creates silver linings in the oddest of places. Researchers can find solutions in strange places when they look at problems from new angles. Sometimes it’s a matter of understanding the variables you’re working with. Sometimes you need to work backwards to find a solution.

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