Critical Genes in "Zombie" Tuberculosis Pathogens Identified
New breakthrough uncovers how to kill "zombie" TB cells resistant to antibiotics.
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Many dangerous pathogens, including the bacteria that cause TB, are capable of generating dormant, drug-tolerant cells often described as ‘zombies’. These persister cells can survive intense antibiotic treatments by essentially playing dead. Once the drugs are gone, they ‘wake up’ and can trigger recurring, and often deadly, infections. Eliminating these zombie-like cells currently requires months of multi-drug therapy –and even then, treatment often fails, fuelling relapse and the rise of antimicrobial resistance (AMR).
In the study, the Surrey team exposed a vast library of over 500,000 genetically modified TB bacteria to two commonly used antibiotics – rifampicin and streptomycin. The exposure was extended long enough that the remaining survivors were primarily persisters. By analysing the survivors, the researchers pinpointed genes whose disruption significantly reduced the number of surviving zombie cells.
These critical genes were found to perform various roles: some weakened the protective bacterial cell wall, others activated a form of bacterial self-destruction and still others disrupted the cell’s metabolic balance. Each of these pathways offers a potential strategy for designing new drugs that could wipe out persister cells more rapidly and effectively.
The next phase of research will focus on developing novel therapeutics that mimic these gene functions – paving the way for shorter, more successful TB treatments and a powerful new weapon in the global fight against AMR.
Mutations in some of the genes identified in the study have been found in TB strains from patients who do not respond to treatment. This overlap suggests that the mechanisms observed in the lab reflect what is happening in real infections and may help explain why some patients relapse even when the bacteria are not resistant to the antibiotics.
Reference: Toloza JEH, Xu Y, Mendum TA, et al. The identification Mycobacterium tuberculosis genes that modulate long term survival in the presence of rifampicin and streptomycin. Sci Rep. 2025;15(1):1-15. doi: 10.1038/s41598-025-04038-9
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