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Member Research and Reports

Johns Hopkins Led Study Uncovers Clues about How Leading TB Drug Attacks Its Target

Researchers at the Johns Hopkins Bloomberg School of Public Health say they have discovered a new clue to understanding how the most important medication for tuberculosis (TB) works to attack dormant TB bacteria in order to shorten treatment.

The antibiotic Pyrazinamide (PZA) has been used to treat TB since the 1950s, but its mechanisms are the least understood of all TB drugs. The PZA findings may help researchers identify new and more effective drugs not only for TB – which can require six months or more of treatment – but other persistent bacterial infections. A report on the research is published online August 13 in the journal Emerging Microbes & Infections.

“PZA is probably the most unique antibiotic we have because instead of only going after TB cells that are actively replicating, it seeks out and destroys dormant TB cells that can’t be controlled by other antibiotics,” says study leader Dr. Ying Zhang, MD, a professor in the Bloomberg School’s Department of Molecular Microbiology and Immunology. “It is like when you are weeding. Most current drugs just chop off the leaves, but the roots are still there. PZA gets at the roots. Learning how it does that may enable us to get rid of TB quicker and more permanently without relapse.”

The new study, done in conjunction with Fudan University in Shanghai, found that PZA cuts off the energy production of Mycobacterium tuberculosis, killing the bacteria. It does this by disrupting the PanD, which, among other things, is crucial to synthesis of co-enzyme A, a molecule at the center of energy metabolism. When PanD is working correctly in a TB cell, it allows the cell to survive and persist despite a long course of treatment. Only PZA’s unique ability to halt this process allows it to clear the dormant bacteria.

Read more: http://www.jhsph.edu/news/news-releases/2014/researchers-uncover-clues-about-how-the-most-important-tb-drug-attacks-its-target.html