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Rockefeller University researchers have built the most detailed genetic interaction map of Mycobacterium tuberculosis (Mtb) ever created, uncovering nearly 6,500 previously unknown gene relationships. Published in Nature, the map could help scientists pinpoint new drug targets and design smarter antibiotic combinations — a major leap forward against one of the world's deadliest infections.
Tuberculosis kills more than a million people every year, and treating it is notoriously slow and complicated — often requiring months of multiple antibiotics, with drug-resistant strains making things even harder. Now, Rockefeller University scientists have taken a major step toward changing that. Using a modified gene-silencing tool called CRISPRi, they built the most comprehensive map ever of how essential genes interact in Mycobacterium tuberculosis (Mtb), the bacterium behind TB. The study was published in Nature.
Instead of knocking out genes entirely (which would kill the bacteria), the team dialed down gene activity — two genes at a time — to see how pairs of genes work together. They also used AlphaFold 3, an AI-powered molecular modeling tool, to deepen their understanding of those interactions at the structural level. The result: a publicly available map that opens up a huge swath of the TB genome that was previously a black box for drug discovery.
By the Numbers:
Why it matters: For decades, TB drug regimens have been developed largely through trial and error. This map gives researchers a systematic roadmap to find better antibiotic combinations faster — and could reveal entirely new drug targets hiding in plain sight.
