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Butler's Researchers Tackle TB
By Cindy Conover Dashnaw
Most of us get a TB test some time in our lives, and we go on our merry way, assuming it will be negative.
We don’t know how lucky we are.
Butler University Associate Professor of Chemistry Jeremy Johnson is searching for a way to spread that luck to the parts of the world where tuberculosis still kills more people than any other infectious disease: 1.5 million annually.
Worse yet, the bacterium causing the disease (Mycobacterium tuberculosis) is becoming increasingly resistant to the antibiotics doctors use to treat the infection.
“The incidence of TB has remained fairly steady over time. It now annually causes more deaths worldwide than HIV, the other major fatal bacterial infection,” said Johnson, the recent recipient of a National Institutes of Health grant to study the disease.
Researchers rightly made a massive push toward arresting HIV growth in the 1980s, with tremendous success. Today, Johnson is part of a growing body of researchers determined to achieve the same success with TB.
“The bacterium that causes TB has a complex life cycle that’s very difficult to treat with current methods: four drugs and six months to treat a full-blown case,” he said. “In the U.S., we have a healthcare system that makes sure patients take their drugs all the way through their treatment schedule. In other countries, people start feeling better and stop taking their medicine, leading to drug-resistant TB infections.”
When TB is in its active form, it’s contagious and transmitted through the air. When it’s dormant – where Johnson is focusing his research – the bacterium exists inside the lungs, kept inactive by a healthy immune system.
Most treatments today don’t target inactive versions of TB. Johnson believes stopping the bacterium at the dormant stage – long before it’s a contagious infection – holds the most promise for eradicating the disease.
Here’s where Johnson gets technical.
“We’re looking at a particular class of enzymes within TB known as serine hydrolases. When researchers looked at the toxic proteins TB produces, they saw that serine hydrolases accounted for twice as many as other toxic bacteria produced – in fact, a higher relative amount of serine hydrolases are made in TB than we make as humans.
“In the change between dormant and active states, the body secretes a large number of these serine hydrolases into a person’s lungs, where they break down the host’s cellular components. TB bacterium then feed on nutrients from those components to survive.
“Our proposal is that if we can inhibit these serine hydrolases from being active during dormancy, then we could stop the entire process. In the dormant state, there is only a very small number of bacterium.”
More than 30 million people have died since the World Health Organization declared TB to be a global emergency in 1993. In 2016, the WHO declared the world is not doing enough to meet its TB goals.
Not if Johnson and his research students at Butler University can help it.
Learn more about the hands-on research happening at Butler here.