Antimicrobial Agents & Resistance

Killing TB in its Dormant Form

Researchers at the University of Sussex in the UK and the Polish Academy of Sciences think they have found a way to make latent tuberculosis (TB) more susceptible to oxidative damage while it is hiding out in the body. The keys are the enzyme complexes Ligase C and Ligase D. The team had previously discovered that Ligase D helps mycobacteria repair their DNA after attack, and their latest work reveals that Ligase C helps Ligase D do its job.

About one-quarter of the world has latent tuberculosis (TB), and one-tenth of that population will develop active disease in their lifetime years or even decades later. Treating the latent bacteria has been unrewarding because the only drugs available produce debilitating side effects in the patient and usually can’t overcome TB’s DNA repair mechanisms.

“Mycobacteria are incredibly resilient and can remain dormant for many years inside cells where they are exposed to significant levels of free radical damage designed to kill foreign invaders,” said Aidan Doherty, leader of the Sussex arm of the team. We have shown that, by removing Ligase C and D, mycobacterial cells become much more sensitive to oxidative damage. With further investigation of these protective mechanisms, [we] hope that this research will pave the way for the development of new drugs to more successfully target mycobacteria.”

Caption: A false color scanning electron microscopy image of Mycobacterium bovis BCG.
Credit: Photo taken by Dr Julian Thorpe of the University of Sussex and Dr Simon Waddell of the Brighton and Sussex Medical School.
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For more information, go to the November 1 issue of Nature Communications; DOI: 10.1038/s41467-017-01365-y.