Culture

New Research to Combat Tuberculosis

As governments deal with the realities of the global pandemic Covid19 it might be forgotten that the world’s single deadliest infectious disease is Tuberculosis (TB).

There are 1.5 million deaths a year worldwide due to TB. In most cases it could be cured by antibiotics although there is evidence of increasing numbers of people resistant to these life saving antibiotics.

TB  is spread by breathing in tiny droplets from the coughs or sneezes of an infected person and mainly affects the lungs though it can affect any part of the body, including the glands, bones and nervous system.

In Scotland and rUK  the BCG vaccine offers protection against TB, and is recommended on the NHS for babies, children and adults under the age of 35 who are considered to be at risk of catching TB.

There are many countries where there is no similar vaccination programme and TB debilitates and kills many people.

You can find the list here: Tuberculosis rates by country in 2018 worldwide_table_

An international team of researchers, led by Durham University, UK, and the Laboratory of Molecular Microbiology and Genetics/Centre Integrative Biology in Toulouse, France, are aiming to exploit a new toxin, called MenT, produced by the TB bacterium Mycobacterium tuberculosis,   to develop new anti-TB drugs.

Co-Senior author Dr Tim Blower, Associate Professor in the Department of Biosciences, and Lister Institute Prize Fellow at Durham University, said:

“Effectively the tuberculosis is actively poisoning itself.

“Through the forced activation of MenT, or by destabilising the relationship between the toxin and its anti-toxin MenA, we could kill the bacteria that cause TB.

“The remarkable anti-bacterial properties of such toxins make them of huge therapeutic interest.”

TB Surface electrostatic representation of toxin MenT (blue, positive; red, negative), showing where target tRNA would bind and the enzymatic active site.

Surface electrostatic representation of toxin MenT (blue, positive; red, negative), showing where target tRNA would bind and the enzymatic active site. CREDIT Ben Usher, Dr Tim Blower.

Eight countries account for two thirds of the total TB cases in the world, with India leading the count, followed by, China, Indonesia, the Philippines, Pakistan, Nigeria, Bangladesh and South Africa.

The World Health Organisation (WHO) recognise that multidrug-resistant TB (MDR-TB) is a public health crisis and a health security threat.

WHO estimates that there were 484,000 new cases with resistance to rifampicin – the most effective first-line drug, of which 78% had MDR-TB.

The aim of the WHO is to end the TB  epidemic  worldwide by 2030. Stats from WHO show that an estimated 58 million lives were saved through TB diagnosis and treatment between 2000 and 2018.

TB is particularly hard to diagnose in children. In 2018, 1.1 million children (0–14 years of age) fell ill with TB, and 230 000 children (including children with HIV associated TB) died from the disease.

The research into the use of the new toxin, called MenT,  also involved The Institute of Pharmacology and Structural Biology, Toulouse, and the Institute of Physico-Chemical Biology, Paris, France; and the University of Otago, New Zealand.

Co-Senior author Dr Pierre Genevaux, CNRS Research Director at the Laboratory of Molecular Microbiology and Genetics/Centre Integrative Biolog, CNRS/Toulouse University, said:

“Our research identifies a previously unknown mechanism that could block protein synthesis and potentially treat tuberculosis and other infections.

“This work opens up new avenues of research and discovery for the next generation of drugs.”

TB Activated MenT toxin stops growth of Mycobacterium tuberculosis, compared to biochemically inactive mutant versions of MenT.

Activated MenT toxin stops growth of Mycobacterium tuberculosis, compared to biochemically inactive mutant versions of MenT. Credit: Dr Claude Gutierrez.

For more information about TB in Scotland click on this download: TB fact sheet February 2020

Reporter: Fiona Grahame

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