Indian-American researcher working to counter global threat of antibiotic resistance

Sriram Chandrasekaran evaluates research on his computer. Image credit: Joseph Xu, College of Engineering, University of Michigan

An Indian-American from the University of Michigan, along with his team of researchers, has discovered the specific mechanism that the body’s T-cells need to use in order to kill bacteria, preventing illnesses.

According to a University of Michigan report, Sriram Chandrasekaran, assistant professor of biomedical engineering at UMich, and Judy Lieberman from Harvard have discovered a key difference between the way immune cells attack bacteria and the way antibiotics do.

As drugs typically attack with a single process within bacteria, T-cells attack a host of processes at the same time and the study shows that there is a potential for drug-resistant pathogens to kill a projected 10 million people annually across the globe by the year 2050.

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, the UMich report says.

“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. 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,” Chandrasekaran is quoted saying in the news story.

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

Chandrasekaran and his team monitored how T-cells deal with three different threats: E. coli, listeria and tuberculosis, using Proteomics, a technique that measures protein levels in a cell, along with computer modeling, this allowed them to see granzyme B’s multipronged attack targeting multiple processes.

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

World Health Organization officials describe antibiotic resistance as “one of the biggest threats to global health, food security and development today” and each year, an estimated 700,000 deaths are linked to antibiotic-resistant bacteria, projections show that the number is to rise to 10 million by 2050.

The UMich report quotes Sally Davies, England’s top health official warning recently that the lost effectiveness of antibiotics would mean “the end of modern medicine. We really are facing—if we don’t take action now—a dreadful post-antibiotic apocalypse. I don’t want to say to my children that I didn’t do my best to protect them and their children.”

In fact, there are only a few new antibiotics in the pipeline now as the heyday of new antibiotics occurred between the 1940s and 1960s, and coming to a halt at the end of the 20th century.

“We’ve reached a point where we take what antibiotics can do for granted, and we can’t do that anymore. We’re taking inspiration from the human immune system, which has been fighting infections for thousands of years,” Chandrasekaran said.



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