New regulatory map may show how to defeat Tuberculosis

Researchers at Stanford University, Seattle BioMed, Boston University and the Broad Institute, Max Planck Institute of Biology, Caprion Proteomics, Inc., Brigham and Woman's Hospital and Colorado State University showed on Wednesday the first comprehensive regulatory map of TB.

The results of the study were published in the journal Nature. This gene mapping of Mycobacterium tuberculosis is a first step towards better understanding the regulatory network for the bacteria.

Before this study, scientists did not have a comprehensive understanding about how the bacterium worked. What confused scientists the most was the way TB could adapt to changing conditions inside the host.

TB, an infectious disease that affects the respiratory system inside the human body, is known for its ability to change inside its host. TB is able to change to resist certain drugs and TB adapt to outdated methods of treatment.

One of these treatments was to reduce oxygen tension by either artificially collapsing a lung or inserting large items into the pleural cavity. These methods worked for a time, but TB showed signs it was able to change and adapt to the hypoxic environments.

"We needed a window into how tuberculosis adapts to change, whether that is a lack of oxygen or a new drug," David Sherman, a lead researcher from Seattle BioMed, said. "In order to do that, we needed to understand how TB is wired -- how its genes and the molecules that regulate them are related -- so we can see how it changes its behavior depending on the environment."

The researchers analyzed how proteins interact with DNA and were able to find 50 of TB's regulatory transcription factors bound to DNA. This gave them the diagram of genetic connections in TB. While a diagram of these connections has been done in the past, this is the first time a complete mapping has been completed all at once.

"Everyone who studies TB can now look at this wiring diagram and gain a better understanding of how their favorite genes relate in a larger context," Sherman said. "Suddenly, we can see how different areas connect, in intimate and important detail."