Chandrasekaran study

Sriram Chandrasekaran is an Indian American biomedical engineering assistant professor at the University of Michigan. (University of Michigan photo)

An Indian American-led study at the University of Michigan could lead to the discovery of a way to fend off the threat of drug-resistant pathogens.

The university wrote in an Oct. 26 report that a study, led by Michigan's Sriram Chandrasekaran and Harvard's Judy Lieberman, discovered the mechanism the body's T-cells use to kill bacteria.

The researchers specifically discovered the integral difference between the way immune cells attack bacteria and the way antibiotics do, according to the report.

Where drugs typically attack a single process within bacteria, T cells attack a host of processes at the same time, the report said.

“We have a huge crisis of antibiotic resistance right now in that most drugs that treat diseases like tuberculosis or listeria, or pathogens like E.coli, are not effective," said Chandrasekaran, a biomedical engineering assistant professor at the University of Michigan, in the report. “So there is a huge need for figuring out how the immune system does its work. We hope to design a drug that goes after bacteria in a similar way.”

Killer T cells, formally known as cytotoxic lymphocytes, attack infected cells by producing the enzyme granzyme B. How this enzyme triggers death in bacteria has not been well understood, Chandrasekaran said in the report.

Proteomics—a technique that measures protein levels in a cell—and computer modeling, allowed researchers to see granzyme B's multipronged attack targeting multiple processes, the report added.

The Chandrasekaran-led research team observed how T cells deal with three different threats: E. coli, listeria and tuberculosis.

"When exposed to granzyme B, the bacteria were unable to develop resistance to the multipronged attack, even after exposure over multiple generations," Chandrasekaran added. "This enzyme breaks down multiple proteins that are essential for the bacteria to survive. It's essentially killing several birds with one stone."

The possible applications of the new findings on T cells run the gamut from the creation of new medications to the repurposing of previously approved drugs in combination to fight infections by mimicking granzyme B, the report added.

The team is now looking at how bacteria hide to avoid T-cell attacks, it said.

"We've reached a point where we take what antibiotics can do for granted, and we can't do that anymore," the assistant professor continued. "We're taking inspiration from the human immune system, which has been fighting infections for thousands of years."

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