Leprosy is a disease that is practically irrelevant in industrialized countries. Those affected suffer from severe skin changes, paralysis and neurological damage. However, disease-causing bacteria may also have potential applications in regenerative medicine: thanks to their ability to genetically reprogram host cells, they can help regenerate the liver. Scientists have now tested this mechanism on armadillos. In the long term, therapies for people with liver damage could be developed on this basis.
Armadillos infected with leprosy
Leprosy is one of the oldest known diseases in the world. It was widespread in Europe in the Middle Ages. Currently, it is mainly found in countries such as Brazil, India and Indonesia. It is caused by Mycobacterium lepra, which spreads mainly under poor hygienic conditions. However, the bacteria can be effectively fought with timely medical therapy with antibiotics. If left untreated, it nests in infected cells and changes them. The consequence of this in the advanced stage is, among other things, noticeable skin tumors, which are typical for the disease.
However, this ability to alter host cells could also open up medical applications. Leprosy bacteria seem to ensure that the liver grows and maintains a healthy structure during this growth. A team led by Samuel Hess from the University of Edinburgh in Scotland has now demonstrated this mechanism in armadillos (Dasypus novemcinctus). These animals are the natural host of the leprosy bacteria.
For their experiment, the scientists infected 32 adult leprosy-prone armadillos with this bacterium. Twelve uninfected animals and 13 leprosy-resistant armadillos that became infected but failed to spread the bacteria served as controls. “Compared to uninfected and resistant animals, the livers of infected armadillos were significantly enlarged within 10 to 30 months“, the researchers reported on their results.
Leprosy stimulates the growth of the liver
“The enlarged infected liver had an intact architecture and vasculature without damage, scarring or tumors”, the researchers continue. The team’s cellular analyzes showed that the infection activated gene expression patterns in the animals’ livers similar to those found in very young animals, stimulating the organ’s metabolism, growth and cell proliferation. At the same time, expression patterns associated with liver aging were reduced or suppressed.
The researchers hypothesize that the bacteria will reprogram the liver cells and return them to their progenitor cell stage. These progenitor cells then develop into new liver cells and new liver tissue. “If we can figure out how bacteria cultivate the liver as a functional organ without causing harmful effects in living animals, we could use this knowledge to design safer therapeutic measures to rejuvenate aging livers and regenerate damaged tissues.” said Anura Rambukkana, who participated in the experiment.
Chances of liver disease?
Liver disease is currently responsible for approximately two million deaths per year. There is often only one way to save the affected: a liver transplant. As with all organ transplants, the problem is the lack of suitable donor organs.
If there was a way to use the leprosy bacteria to regrow the remnants of liver disease into a healthy organ, many of these deaths could be avoided. The bacterium could open up promising approaches for regenerative medicine. However, infecting patients from the liver with leprosy is of course out of the question – the side effects (specifically leprosy infection) would be too strong. However, there may be an opportunity to copy the mechanisms underlying liver growth. “The bacterial genome is a valuable resource for future studies“explain the researchers.
through the University of Edinburgh