By creating the first comprehensive map of the genetic framework controlling tuberculosis bacteria, scientists may have taken a significant step towards defeating one of the deadliest diseases in human history. Researchers from Stanford University, Seattle BioMed, Boston University and the Broad Institute, Max Planck Institute of Biology in Berlin, Germany, Caprion Proteomics Inc. in Montreal, Canada, Brigham and Woman's Hospital (Harvard University), and Colorado State University have traced the regulatory network of the condition, in an effort to understand the processes whereby Mycobacterium tuberculosis – the causative agent in tuberculosis infections – adapts and survives within the host.
In the centuries preceding the rise of antibiotics, rudimentary treatment programs often relied on the perceived association between oxygen tension and bacteria control, as the infection is commonly centered in the pulmonary system. However, the tuberculosis bacteria somehow seemed to survive in the host, even when partial hypoxia was induced.
"We needed a window into how tuberculosis adapts to change, whether that is a lack of oxygen or a new drug," said David Sherman, Ph.D., a lead researcher from Seattle BioMed. "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."
In identifying the key genes necessary to understand the condition’s regulatory network, the researchers relied on a piece of technology known as ChIP-Seq – an analytical tool used to assess the interaction between proteins and DNA, which ultimately allowed the team to derive a wiring diagram of the bacterium’s genetic connections.
While such assessments have been done in the past, the comprehensive scope of the study makes it unique. "Nobody has ever done ChIP-Seq for every transcription factor in an organism," Sherman explained. "This is a far more global view of one organism's wiring than anyone has ever achieved before."
The research will likely underpin future efforts to develop more advanced treatment programs for the condition, as the results are relevant to virtually anyone studying the bacterium. "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," said Sherman. "Suddenly, we can see how different areas connect, in intimate and important detail."
Eventually, the genetic “roadmap” will provide insight into how targeted drugs and immunological interventions could shut down the infection by impairing the bacteria’s ability to survive within the host’s body.