A key difference between the way immune cells attack bacteria and the way antibiotics do may provide a roadmap for combatting the rising threat of drug-resistant pathogens.
Researchers of the University of Michigan (UM), in collaboration with colleagues at Harvard University, have discovered that while drugs typically attack a single process within bacteria, T cells attack a host of processes at the same time.
The findings have been newly published in the journal Cell.
"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, UM assistant professor of biomedical engineering. "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.
Chandrasekaran and his team monitored 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 said. "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 range from the creation of new medications to the repurposing of previously approved drugs in combination to fight infections by mimicking granzyme B.
World Health Organization (WHO) officials describe antibiotic resistance as "one of the biggest threats to global health, food security and development today."
WHO data show that an estimated 700,000 deaths are linked to antibiotic-resistant bacteria each year. Projections show that number will skyrocket to 10 million by 2050.
Of particular concern is the fact that there are few new antibiotics in the pipeline. The heyday of new antibiotics occurred in the 1940s through the 1960s, with releases eventually grinding almost to a halt by 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," Chandrasekaran said. "We're taking inspiration from the human immune system, which has been fighting infections for thousands of years."