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Mapping the Genetic Networks of Tuberculosis to Understand Its Biology and Develop Better Treatments

Jeremy M. Rock, PhD, Associate Professor and Head of the Laboratory of Host-Pathogen Biology, Rockefeller University

Tuberculosis (TB) remains one of the world’s deadliest infectious diseases, and treatment still requires multiple antibiotics taken over many months. Developing better therapies will require a deeper understanding of how the bacterium that causes TB, Mycobacterium tuberculosis, functions and how its genes work together.

Researchers at The Rockefeller University developed a powerful new approach to systematically map these genetic relationships. Using CRISPR interference, a technology that allows scientists to selectively reduce gene activity, the team studied how disrupting pairs of genes affects bacterial growth. By focusing on genes essential for survival, they uncovered thousands of previously unknown genetic interactions, creating the first comprehensive map of its kind in a bacterial pathogen.

The map provides new insights into the fundamental biology of TB, including the identification of previously mysterious genes involved in bacterial energy production. Just as importantly, it offers a new strategy for developing better treatments. By identifying pairs of genes whose simultaneous disruption is especially harmful to the bacterium, researchers predicted and experimentally validated several promising antibiotic combinations.

This publicly available resource could help researchers identify new drug targets and design more effective combination therapies against TB, providing an important foundation for future efforts to combat the disease.

A new map charts interactions among nearly all essential genes in M. tuberculosis.

Read the full article in Nature.