Leprosy can cause severe skin changes, paralysis and neurological damage. The bacteria that cause the disease may also have medically useful properties: their ability to genetically reprogram host cells could help regenerate the liver. Using armadillos, researchers have demonstrated that the livers of individuals infected with leprosy grew while maintaining their healthy structure. Further insight into the tricks of the bacteria could help to develop regenerative therapies for people with liver damage.
Leprosy is one of the oldest known diseases in the world. Also known as leprosy, it was widespread in Europe in the Middle Ages. Today it is mainly found in countries such as India, Brazil and Indonesia. The cause of this infectious disease is the Mycobacterium lepra. It spreads primarily under poor hygiene conditions, but can be effectively combated with timely treatment with antibiotics. If left untreated, however, it nests in the infected host cells and changes them. In the advanced stage, this leads to stigmatizing skin tumors, disturbances of the sense of touch and paralysis.
Armadillos with leprosy
However, the ability to change the host cells could possibly be medically helpful: In the liver, the Mycobacterium lepra apparently ensures that the organ grows while maintaining its healthy structure. A team led by Samuel Hess from the University of Edinburgh in Scotland has now demonstrated this in armadillos (Dasypus novemcinctus). The mammals native to the New World are a natural host of the leprosy bacterium.
Hess and his colleagues infected 32 adult armadillos susceptible to leprosy with the pathogen. Twelve uninfected individuals and 13 leprosy-resistant armadillos, which were also infected but in which the bacterium could not spread, served as control groups. “Compared to uninfected and resistant animals, the livers of the infected armadillos significantly enlarged within ten to 30 months,” the researchers report. The infected individuals showed high bacterial counts in the liver.
growth without damage
The remarkable thing about it: “The enlarged infected livers had an intact architecture and vascular organization without damage, scarring or tumors,” according to the researchers. Cell analysis showed that in the infected livers, gene expression patterns similar to those seen in very young animals had been activated: genes related to metabolism, growth, and cell proliferation were activated, and those related to aging were downregulated or suppressed.
The authors suspect that the bacteria reprogrammed the liver cells, returning them to the earlier stage of progenitor cells, from which new liver cells can develop and new liver tissue grows. This has the advantage for the bacteria that there is more tissue in which they can spread. “If we can figure out how bacteria grow the liver as a functional organ without causing harmful effects in living animals, we may be able to use this knowledge to develop safer therapeutic measures to rejuvenate aging livers and regenerate damaged tissues,” says Hess ‘ Colleague Anura Rambukkana.
Help with liver diseases?
Liver diseases currently lead to around two million deaths worldwide every year. In many cases, a transplant is the only way to save the patient. If it were possible to regrow what was left of the patient’s own liver into a healthy organ, many liver-related deaths could probably be avoided. However, earlier studies that attempted to regenerate mouse livers with the help of implanted stem cells were not very successful: scars and tumors formed in many cases.
The Mycobacterium lepra could open up promising new approaches: Even if it is out of the question to deliberately infect patients with damaged livers with leprosy due to the severe symptoms of the disease in humans, the mechanisms used by the bacterium could possibly be copied for therapies. “The bacterial genome is a valuable resource for future studies,” say the researchers.
Source: Samuel Hess (University of Edinburgh, Scotland) et al., Cell Reports Medicine, doi: 10.1016/j.xcrm.2022.100820