New research from the University of Surrey and the University of Oxford has uncovered a reversible mechanism in TB bacteria that may explain why the disease is so hard to treat.
The study shows that Mycobacterium tuberculosis uses a process called ADP-ribosylation to tag its DNA, allowing it to pause or resume growth—a possible survival tactic against antibiotics and immune attacks. The enzymes DarT and DarG act like a molecular switch: DarT adds the tag and halts replication, while DarG removes it to restart bacterial growth.
This discovery marks the first time DNA modification has been shown to control gene expression and replication in any organism.
By manipulating this system using CRISPRi and ADPr-Seq, scientists were able to track how these tags affect gene activity and cell division, offering a new target for drug development, especially against dormant or slow-growing TB cells. With over 1.25 million deaths annually, breakthroughs like this could reshape how we treat one of the world’s deadliest infectious diseases. Learn more here.