Study discovers DNA switch that controls TB growth – and could help unlock its antibiotic resistance secrets

The study focused on two enzymes: DarT, which adds the ADP-ribose tag to DNA, and DarG, which removes it. When DarT is active, it stops the bacteria from copying their DNA and dividing. When DarG removes the tag, growth resumes. This start-and-stop control may help the bacteria survive in harsh conditions, making them more resilient during long-term infections.  

To find out more about how this molecular switch works, the researchers used a CRISPR interference (CRISPRi) system to selectively reduce levels of DarG. This allowed DarT to act without restraint, leading to the build-up of DNA modifications and halting bacterial growth. The team then used a technique called ADPr-Seq to map where these tags appeared across the genome, alongside live-cell imaging and RNA sequencing to track changes in DNA replication, cell division and gene expression. These tools helped reveal how ADP-ribosylation affects both the ability of the bacteria to replicate and the activity of genes needed for survival in stressful environments. 

According to the World Health Organization, TB kills 1.25 million people globally every year. In 2023, around 10.8 million people fell ill with the disease.