The bacteria that cause leprosy have been found to reprogram liver cells in armadillos and make the organ regrow, offering clues that could lead to new treatments
The bacteria that cause leprosy can reprogram liver cells to grow new tissue, an ability that may help to develop treatments to rejuvenate ageing and diseased livers.
Leprosy is caused by slow-growing bacteria called Mycobacterium leprae, which can infect the nerves, skin, eyes and nose, leading to the condition’s main symptom of severely disfiguring sores, lumps and bumps.
Anura Rambukkana at the University of Edinburgh in the UK and his colleagues have discovered that M. leprae performs what they call “biological alchemy” in order to grow and spread through host tissue.
In 2013, they reported that M. leprae hijacks the genes of Schwann cells, which form a fatty substance that insulates peripheral nerve fibres. The bacteria reactivate developmental genes, causing the Schwann cells to revert to a migratory, stem cell-like state and move around the body, enabling the bacteria to infect more cells.
In their latest study, Rambukkana and his colleagues show that M. leprae can similarly “reprogram” liver cells, too.
“Leprosy bacteria can grow the liver tissues at organ level and this could translate to develop therapies that could replace liver transplantation,” says Rambukkana.
The researchers infected nine armadillos, the natural host of leprosy bacteria, and found that infection reprograms the entire liver into a developmental state.
Infected animals had significantly larger livers containing large numbers of dividing immature liver cells, as well as a proportionate expansion of blood vessels and biliary ducts, which produce, store and secrete bile.
Importantly, the enlarged livers were perfectly healthy, showing no signs of thickening, scarring or tumour growth. Infection also activated anti-ageing genes and deactivated those associated with ageing.
Tissue reprogramming is a promising area of research in regenerative medicine, but there are major safety concerns. A widely used method for turning mature cells into stem cells in the lab can cause aggressive cancers, says Rambukkana. “In contrast, our humble leprosy bacteria naturally induce partial reprogramming of adult tissues.”
Unlocking the secrets of M. leprae could therefore help to develop safer reprogramming methods.
“This study provides a new tool to study liver rejuvenation and regeneration,“ says Luca Urbani at the Roger Williams Institute of Hepatology in London. “It may help us to understand how to activate liver regeneration and growth in a safe way, maintaining intact organ structure and functionality without the development of unwanted effects, such as tumour formation and scarring.”
Journal reference: Cell Reports Medicine, DOI: 10.1016/j.xcrm.2022.100820
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