ISU researchers find clue to stopping tuberculosis

Steph Luhring

In 2009, researchers at Iowa State found a chemical that inhibits the human immune system from killing the bacteria that causes tuberculosis. Now they are working to find an enzyme that will inhibit this chemical instead.

Mycobacterium tuberculosis is the bacteria that causes tuberculosis. It is a pathogen, which means it can be spread through the air when an infected person coughs and another person breathes it into their lungs, according to Reuban Peters, leader of Iowa State’s team of scientists dedicated to this research. When the human body’s immune system recognizes the foreign bacteria, sentinel cells try to “eat the bacteria and kill it inside the cell,” Peters said.

In December of 2005, researchers began work on a clue that could lead to understanding tuberculosis and the immune system. They collaborated with teams from the University of Illinois, Urbana-Champaign and Cornell University, Ithaca, New York.

“We discovered something the bacteria makes, a chemical,” Peters said.

The chemical was Isotuberculosinol, which is a natural product that aids in blocking the killing function of sentinel cells of the human body’s immune system.

“We kind of stumbled upon it,” said Francis Mann, a recent graduate and doctoral student who was part of the research team.

A Japanese group of researchers were the first to discover that mycobacterium tuberculosis made the chemical.

Peters speculated that the mycobacterium tuberculosis bacteria may have picked up the genes for Isotuberculosinol from a plant. The ancestral mycobacterium tuberculosis may have originated in the soil where it would be in contact with rotting plant material.

Peters said they discovered how the bacteria makes Isotuberculosinol and what triggered the compound.

“Now we have some clues [showing] how to block the production of Isotuberculosinol,” Peters said.

Now the research team is working to “find a suitable inhibitor to allow macrophages to kill mycobacterium tuberculosis” said Meimei Xu, an associate scientist on the research team.

Mann said that by feeding Isotuberculosinol to molecules in the immune system, the immune system is arrested. The researchers are trying to “design an analog that mimics mycobacterium” to help find where the bacteria binds to cells.

Peters said the next step is to put tags on the Isotuberculosinol chemical so that they can “pull it out and hopefully it will still be attached to what it is binding to.”

There are 10 million new cases of tuberculosis a year, and the disease causes close to 1.5 to 1.8 million deaths per year, Peters  said.

“We’re discovering not only how a pathogen manipulates our immune system … we hope that it will tell us how the immune system works as well,” Peters said.