Who might hold the key to eradicating tuberculosis?

By Mark Waghorn via SWNS

Jewish people could hold the key to eradicating tuberculosis - one of the world's biggest killers, according to new research.

Many Jewish people are less susceptible to the deadly bacterial infection because of a rare genetic disorder.

It could lead to better vaccines for a disease that claimed 1.6 million lives in 2021.

Co-author Professor Timothy Cox of Cambridge University said: "Our discovery may provide clues to possible new treatments for TB.

"Drugs that mimic the effects of Gaucher disease – specifically the build-up of glucosylsphingosine – might offer antimicrobial effects against TB.”

Several such drugs have already been designed by colleague Prof. Hans Aerts at Leiden University.

They would only need to be administered for a relatively short amount of time so any side effects should be limited and temporary.

Gaucher disease affects one in 40,000 to 60,000 births in the general population.

But cases rise to one in 800 among Ashkenazi Jews whose ancestors lived in France, Germany, Poland and Russia.

Common symptoms include an enlarged spleen and liver and anemia. Around two-thirds of people carrying two copies of the most common genetic variant are unaware they are carriers.

Experiments on zebrafish found the same biological mechanisms that underlie Gaucher disease are also effective at clearing TB infection.

The humble creature - a popular addition to household aquariums - is relatively easy to manipulate and has a similar immune system to humans.

When co-author Proffesor Lalita Ramakrishnan and colleagues modeled Gaucher disease, zebrafish became resistant to TB.

They genetically engineered them with genetic variants that cause the condition in Ashkenazi Jews.

White blood cells called macrophages became enlarged and unable to break down toxic fats called sphingolipids.

But when the team exposed the fish to TB, they unexpectedly realized they did not become infected.

The fatty chemical that accumulates within the macrophages, called glucosylsphingosine, acted as a detergent-like microbicide.

It kills TB bacteria within minutes by disrupting their cell walls.

Professor Ramakrishnan of Cambridge University said: "We'd unknowingly landed in a debate that's been going on in human genetics for decades.

"Are Ashkenazi Jews - who we know are at a much greater risk of Gaucher disease - somehow less likely to get TB infection? The answer appears to be yes."

Ashkenazi Jews have experienced centuries of persecution. They were often forced to live in ghettos and migrate from country to country.

They would almost certainly have been exposed to TB, which spreads more widely among poorer living conditions and densely-populated urban areas.

The mutation making people more resistant to TB would likely have outweighed the potential fitness cost of Gaucher disease.

This would have increased the likelihood of affected individuals passing on their genes to future generations - spreading the variant within the population.

A similar phenomenon is seen among some individuals who carry genetic variants that protect them from malaria but cause harmful anemia or even sickle cell disease when more than one copy is present.

Only individuals who carry two copies of the Gaucher genetic variant - one from each parent - are likely to be protected against TB.

One "healthy" gene generates enough of the enzyme to clear the macrophages of their accumulating material.

Worldwide, TB is the 13th leading cause of death and the second leading infectious killer after COVID-19 - above HIV.

In 2021, an estimated 10.6 million people fell ill - including 1.2 million children. TB is present in all countries and age groups.

The study is in the Proceedings of the National Academy of Sciences.