New tactic against leprosy

Leprosy has existed at least since Biblical times, but exactly how Mycobacterium leprae causes the symptoms of the disease is still unknown. Although today antibiotics can treat the disease, researchers are concerned about the increase in drug-resistant strains.

Thousands of people are currently affected by leprosy (also known as Hansen’s disease), according to the World Health Organization. The disease can cause skin lesions, nerve damage, and paralysis.

The increase in drug-resistant strains of Mycobacterium leprae has led scientists to search for new treatment options.

As a first step, the researchers have begun to decipher the exact way in which the bacteria interact with the immune system.

The cell walls of mycobacteria such as M. leprae have a thick lipid layer that contains glycolipids (a combination of sugar and fat molecules), which the human immune system can recognize and act against.

For this reason, the team consisting of, among others, Shigenari Ishizuka and Sho Yamasaki, from Osaka University in Japan, and Jeroen DC Codée, from Leiden University in the Netherlands, set out to find out exactly which glycolipids are responsible. of leprosy symptoms and how they interact with the immune system.

The team extracted and synthesized the glycolipid complexes from M. leprae, then exposed them to reporter cells expressing immune receptors.

The component that activated the most cells was PGL-III, a precursor of the most common glycolipid in bacteria, PGL-I.

Microscopic image of a tissue sample from a leprosy patient. A cutaneous nerve has been invaded by numerous bacteria of the species Mycobacterium leprae. (Photo: CDC/Arthur E. Kaye)

The team also found that this glycolipid used only its terminal sugar to bind to an immune receptor called Mincle, a unique interaction not previously known. Furthermore, when mice without the Mincle receptor were exposed to M. leprae, they experienced worse infections than those with the receptor, suggesting that it plays an important role in the natural immune response against leprosy infection.

Therefore, a leprosy treatment targeting this receptor or the PGL-III glycolipid could offer an alternative to the current method that uses a large number of antibiotics. Furthermore, the researchers say that the special relationship between structure and activity between Mincle and PGL-III could be replicated to create other immunostimulatory drugs in the future.

The study is titled “PGL-III, A Rare Intermediate of Mycobacterium Leprae Phenolic Glycolipid Biosynthesis, Is A Potent Mincle Ligand”. And it has been published in the academic journal ACS Central Science. (Source: American Chemical Society)