This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Rockefeller scientists have created the most comprehensive map to date of how essential genes interact in Mycobacterium tuberculosis (Mtb), the bacterium responsible for tuberculosis (TB). The unprecedented map reveals thousands of previously unknown genetic relationships, offering a new window into the inner workings of one of the world's deadliest pathogens.
The work, led by researchers in Jeremy Rock's Laboratory of Host-Pathogen Biology and published in Nature, sheds light on the functions of poorly understood genes and gene interactions. By revealing how genes essential to the bacterium's survival work together, the findings could help scientists identify promising new drug targets as well as develop more effective combinations of antibiotics to combat TB. "Yeast geneticists have used a similar approach to transform our understanding of fundamental cell biology; ever since I started working on TB, I've dreamed of bringing this idea to the study of Mtb," says Rock.
"Now, we have the first comprehensive map of interactions among essential genes in a pathogen. The potential impact for fighting this disease is enormous." Tuberculosis has plagued humanity for thousands of years, and despite decades of medical advances, it remains one of the world's deadliest infectious diseases, claiming more than a million lives each year. That's largely because Mtb is notoriously difficult to eradicate.
For one, the microorganism has a particularly sturdy cell wall that creates a barrier against antibiotics, and its ability to persist in the body makes infections especially stubborn. "It's slow to grow, but it's also slow to die," says Isaac Kresse, a co-first author of the study and graduate fellow in the lab. "And the longer it takes to clear the infection, the more time bacteria have to gain resistance." Treating tuberculosis typically requires multiple antibiotics taken over several months; drug-resistant infections can take even longer to clear from the body.
Finding better treatments, however, requires a deeper understanding of the bacterium itself. Despite decades of research, scientists still don't fully understand the functions of many genes essential to its survival, much less how those genes work together. "There are a lot of genes in the Mtb genome that are just completely uncharacterized," says Natalie Sayegh, a co-first author and Rock lab biomedical fellow.
"We don't know what they do." The researchers' new map takes a major step toward filling that gap. Their ambitious project required systematically studying how hundreds of genes affect one another; it uncovered thousands of previously unknown genetic relationships, offered new clues about gene function, and identified drug-target interactions that could point toward more effective therapeutic combinations. Scientists had long known which genes are essential to the survival of Mtb.
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