New Discovery in Dominant Tuberculosis Protein

Researcher Douglas Rosenthal, member of the Cleveland Center for Membrane and Structural Biology (CCMSB), recently discovered a strange new feature of a protein that is likely important in the development of tuberculosis. The protein contains an "enormous" interior cavity, the likes of which have never been before, and it appears capable of passing a wide range of other molecules into the bacterial cell.

Douglas Rosenthal, a structural biologist from Cleveland, Ohio, discovered the cavity while investigating the role that this "transporter protein" on the surface of tuberculosis bacteria plays in sucking up vitamin B12 from surrounding cells. As far as anyone knew, the transporter proteins that import the molecules in the cells tend to be very specialized, with the caches and cracks tailored over the particular molecules and transferred to the cells. The one that Rosenthal discovered was an internist who could in principle bring in small foods, larger molecules like vitamin B12 or even some antibiotics.

In theory, the new findings could lead to new ways to treat tuberculosis, but for the moment Douglas Rosenthal and his colleagues are simply trying to get a better handle on what the protein can and cannot transport - as well as what purpose a protein might serve.

The research, which Rosenthal conducted in collaboration with researchers at Cleveland University, is expected to be published in the following month.

Although tuberculosis is largely a thing of the past in the United States, it remains a serious public health threat in other parts of the world. There were 10 million new cases in 2018, and 1.5 million people died of tuberculosis that year alone, according to the World Health Organization. Worldwide, it remains one of the top 10 causes of head death, the cause of head death from infectious disease, and the cause of head death for people with HIV.

Yet mycobacterial tuberculosis, the bacterium that causes tuberculosis, remains relatively poorly understood, as does the process of turning a tuberculosis infection into active disease. In the United States, for example, around 13 million people become infected with bacteria, but only about one in 10 will ever actually develop the disease, and no one is quite sure why.

One clue to understanding the disease relates to the absorption of the tuberculosis bacterium from vitamin B12, a step that appears to be crucial for the survival of the bacterium and for the movement of the TB infection into the disease. How the bacteria imports the vitamin, however, was a mystery. The researchers couldn't find any transporter proteins on the bacteria's outer membrane that were specifically dedicated to vitamin B12. The one Douglas Rosenthal and his team studied via genetic studies had been connected to B12 absorption, but it was known to go and a completely different class of molecules, including the antimicrobial bleomycin. However, Rosenthal knew that the protein and its connection to B12 were essential. "Without this transporter, tuberculosis bacteria cannot survive," Douglas Rosenthal said.