Lepra bacillus helps with liver regeneration

Bacteria that cause leprosy may help regenerate healthy livers, write Scottish scientists in the magazine Cell Reports Medicine. They discovered that armadillos with leprosy have a larger liver than armadillos without leprosy, without any scarring or tumor growth in those livers, for example. But before the leprosy bacteria could possibly regenerate human livers, a lot of additional research is needed.

Leprosy is an infectious disease that can have serious consequences in humans. Left untreated, the disease can cause serious facial and limb deformities in a proportion of patients and can also affect nerves. The culprit is the bacteria Mycobacterium leprae. Other animals are also susceptible, including the nine-banded armadillo Dasypus novemcinctus from South and Central America. The armadillo also develops skin and nerve disorders after being infected.

Livers are the most suitable for regeneration of all human organs. That makes organ donation relatively easy; the donor donates part of his or her liver, after which the remaining part grows back into a complete organ within a few weeks.

But the bad news is that in people with liver disease, this regeneration does not take place so naturally: internal scar tissue (such as in cirrhosis of the liver) or tumor growth often develops. And if a liver has to repair itself very often, the process eventually stops and there is no other option than transplantation.

For this reason, the Scottish researchers are now particularly interested in the liver enlargement of infected armadillos, in which the liver is up to four times as heavy as usual (290 instead of 70 grams) and functions healthily. Regeneration biologist Anura Rambukkana, one of the authors, came across the phenomenon when he saw in 2013 how leprosy bacteria are able to ‘hijack’ the plasticity and regenerative properties of so-called Schwann cells. Those cells are located around nerve cells, but are passed through Mycobacterium leprae partially reprogrammed to behave like stem cells. And it is precisely stem cells that can grow into organs. That research was done in petri dishes, with cells from mice.

“The discovery occasionally kept me awake in the years that followed,” says Rambukkana – who once started his research on leprosy bacteria as a student in Amsterdam – by e-mail. “And one night I thought: In Louisiana, leprosy bacteria have been cultured in armadillo livers for decades for research purposes. Wouldn’t there be something wrong with those livers? So I called a researcher friend there and casually asked if he ever noticed anything unusual about the armadillos. And then he started talking about those enlarged livers on his own! That strengthened my suspicion that we might also see the ‘biological alchemy’ we saw in the petri dishes in living animals.”

Thus, Rambukkana and his colleagues began the current study. To do this, they infected 45 armadillos and used 12 as a control group. Under the influence of the leprosy bacteria, the hepatocytes, special liver cells, also started to behave like a kind of stem cell. This caused the livers of infected armadillos to enlarge, but to retain all vital functions. In addition, genes associated with aging were suppressed, while genes associated with growth were activated.

Exactly what useful applications the discovery may have for medicine still needs further investigation. “If we can figure out how the bacteria can reprogram and regenerate the liver, then we might be able to apply that method to humans as well,” says Rambukkana. “But we are not there yet.”