Breaking TB’s Defenses

Tuberculosis in the lung. Prett, no?

Our bodies are in a constant evolutionary war. As with every other living organism on the planet, an arms race is constantly being waged between pathogens and the enzymes, cells or bacteria sent to destroy them. When one side utilizes a new mutation that allows it to thrive, it spreads throughout the population until the trait becomes common. It is then up to the opposing side to develop defenses against the new weapon.

But sometimes it doesn’t quite work out that way. Sometimes one side springs a trap that the other side can’t keep up with. Sometimes Europeans land in North America.

So it is with Mycobacterium tuberculosis. Throughout the ages, this deadly pathogen has been a thorn in the lungs of humans. Nearly one-third of the world’s population is infected with the bacteria. And though only 5-10 percent of them will become symptomatic, it is deadly if left untreated. To make matters worse, there is no vaccine against TB.

For hundreds if not thousands of years, TB has remained unaffected by our bodies’ immune systems, but nobody knows exactly why. Now, thanks to a new study appearing in the journal Structure from the University of Michigan, that is a mystery that may be solved.

The structure of the inactive protease.

When our bodies become infected by a foreign invader, it sends white blood cells to destroy the enemy entity. To do this, the cell envelops the intruder and subjects it to an extremely hostile acidic environment rich in oxidants and other extremely volatile chemicals. But TB has a defense; one that seems to be amplified when TB is subjected to the harsh environment.

In the study led by Oleg Tsodikov, assistant professor in the College of Pharmacy, the researchers imaged the structure of the protein Rv3671c; a protease, meaning that it cuts up other proteins. The exact method it uses to protect its maker TB is unknown, but the studies’ authors suggest it may destroy the harmful proteins that build up in the hostile environment of the white blood cells.

Images were taken both when TB was in a protective mode brought on by exposure to the hostile environment and when it was in a relaxed mode. Whatever its exact mechanics, the team found a difference in the structure of the active protease versus the inactive version. If they could develop a drug that forces the protease into its inactive form, it is quite possible that the bodies’ immune system would do the rest of the work and destroy the deadly invader.

If our own biology refuses to develop its own defenses against a disease, we have luckily evolved another way to build our defenses; a complex nervous system.



About bigkingken

A science writer dedicated to proving that the Big Ten - or the Committee on Institutional Cooperation, if you will - is more than athletics.
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