A protein that acts as a 'control switch,' preventing Mycobacterium tuberculosis from accessing the energy sources it needs to survive, has been identified by researchers at the University of Surrey. The discovery points to a specific vulnerability in the bacterium that could be targeted by new tuberculosis (TB) treatments.

TB remains a major global health threat. It is estimated that around 25 per cent of the world’s population carries latent TB infection, and in 2023 alone there were more than 11 million active TB cases and 1.3 million deaths. A key to Mycobacterium tuberculosis success is its remarkable metabolic flexibility, which allows it to use a wide range of nutrients found inside the human body.

This large study, which involved scientists at Surrey, Imperial College London, the University of Birmingham, Indian Institute of Science and the University of California Irvine, has discovered a unique regulatory protein that acts as a molecular ‘control switch’ enabling M. tuberculosis to access crucial energy sources it needs to survive in the host and to cause disease.

Dr Jane Newcombe, a Research Fellow at the University of Surrey and lead author of the paper said:

“Tuberculosis continues to be a largely uncontrolled pandemic that disproportionately impacts society’s most marginalised populations.

“Sadly, it receives only a fraction of the funding and resources allocated to diseases that affect individuals across all socioeconomic levels equally and as a result our basic understanding of this pathogen still lags behind.”

Using biochemical and systems-level analyses, the team identified an enzyme they have named Virulence Associated DiKinase (VadK). VadK plays a critical role in the metabolism of nutrients, including those that are essential for bacterial survival in the host, and is required for the bacterium to cause tuberculosis.

Co-author Dr Tom Mendum from the University of Surrey, who proposed the name VadK, explained:

“Our work shows that this enzyme has effectively changed its job. VadK has evolved from a metabolic enzyme called pyruvate phosphate dikinase into a specialised regulator that helps the TB bacterium thrive during infection.”

By constructing evolutionary trees, the researchers also found that VadK like enzymes appear to have evolved independently multiple times in other bacterial pathogens. This suggests that VadK, or related proteins, may contribute more broadly to bacterial virulence and could represent a common weak spot that future antibiotics might target.

This study was published in the journal: EMBO Reports