How most vital TB drug attacks its target revealed

A new study has provided a better insight into the mechanism behind the key medication of tuberculosis (TB) attacking the dormant TB bacteria in order to shorten treatment.

Researchers at the Johns Hopkins Bloomberg School of Public Health revealed that 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 might help researchers identify new and more effective drugs not only for TB which could require six months or more of treatment but other persistent bacterial infections.

Ying Zhang, MD, said that PZA was probably the most unique antibiotic 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.

The study 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, was crucial to synthesis of co-enzyme A, a molecule at the center of energy metabolism. When PanD was working correctly in a TB cell, it allowed 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.

Now that the role of PZA on PanD and cells that persist long after treatment has been understood, researchers plans to search for compounds that target PanD in the same way. The findings could have implications for developing drugs that target persistent organisms in other bacterial infections where dormant cells are known to re-emerge such as Lyme Disease, urinary tract infections and even cancer.

The research is published in the journal Emerging Microbes and Infections.