Progression towards new treatments for tuberculosis

New research has discovered how cells infected with tuberculosis bacteria can die, and using new medicines to boost particular forms of cell birth decreased the severity of the disease in a preclinical model.

Tuberculosis generally affects the lungs, but can also affect other parts of the body. In 2018, there were more than 10 million cases of active TB, resulting in 1.5 million deaths and making it the number one cause of death from an infectious disease at that time. A challenge in the fight against tuberculosis is that the bacteria that cause the disease have developed resistance to most antibiotic treatments, leading to a need for new treatment approaches.

One of the ways that cells protect against these 'intracellular' pathogens is to undergo a form of cell death called apoptosis which destroys the cell as well as the microbes within it.

Using preclinical models the researchers demonstrated that a noticeable percentage of tuberculosis-infected cells could die by apoptosis, opening up new opportunities for controlling the disease.

"When we treated our infection models with this compound, we were able to significantly reduce the amount of tuberculosis disease," he said.

The research team was able to duplicate these results using various IAP inhibitors.

"Unlike antibiotics, which directly kill bacteria, IAP inhibitors kill the cells that the tuberculosis bacteria need to survive," he said.

"The beauty of using a host-directed therapy is that it doesn't directly target the microbe, it targets a host process. By targeting the host rather than the microbe, the chances of resistance developing are incredibly low."

"This research increases our understanding of the types of immune responses that are beneficial to us, and this is an important step towards new treatments for tuberculosis, very few of which have been developed in the last 40 years," Dr. Stutz said.

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