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Breakthrough in Tuberculosis Treatment Comes in the Form of Bacterial Proteins

Tuberculosis (TB) is a growing health problem that affects millions of people across the world. Just six countries account for 60 percent of the world’s total TB cases, including India and China. But now that we know it’s both curable and treatable more targeted medicines can be prescribed and we can get a hold of this growing health concern before it gets us.


Research carried out by a team of Rockefeller scientists in collaboration with scientists at Memorial Sloan Kettering focused on RNA polymerase, which is a cluster of interacting proteins that is crucial to all cells. This cluster is responsible for the copying of the genes within DNA into RNA. Elizabeth Campbell, lead researcher for the Rockefeller team and senior research associate in Seth Darst’s Laboratory of Molecular Biophysics, said, “Now that we can visualize the molecular machinery of the bacteria that the drug targets, we can use a structure-guided approach to better understand how the drug works, how bacteria became resistant to it, and how to potentially improve the drug’s action.”

During the study, researchers used x-ray crystallography to visualize the structure. They found that by crystallizing the enzymes and other molecules while they interacted with each other the team could better see how the components all come together to work. By being able to see these reactions happening, researchers can work on producing more effective drugs. Campbell said, “Based on the findings reported in this study we’re already investigating new compounds with new mechanisms of action that appear to inhibit the rifampicin-resistant version of TB. Our eventual goal is to get them into clinical trials investigating new treatments for TB, including rifampicin-resistant TB.”


Statistics estimate that as many as one-third of the world’s population is infected with M. tuberculosis (the TB-causing bacterium). The strain of TB that the team worked most closely with during the study was called M.smegmatis. But, this particular strain relies on an RNA polymerase that’s almost identical to that of the M. tuberculosis RNA polymerase which led to another significant finding: The RNA polymerase from Escherichia coli is not similar, yet is currently being used most often in labs. This could mean that important treatments are being left undetected.

“Most of the studies previously done with RNA polymerase were done using E. coli.  We’ve always assumed that the enzyme works the same way in all bacteria, but our study shows we can’t assume what’s found in one bacteria applies to all bacteria”, says Campbell.  She also confirmed that every individual pathogen will now need to be studied individually, so there’s a lot of work for the team to be moving forward with.


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