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Drug-resistant tuberculosis tricks immune system, say Wash U researchers

Wash U graduate student Nicole Howard works in a biosafety cabinet with the bacteria that cause tuberculosis, while Shabaana Khader looks on.
Matt Miller | Washington University
Wash U graduate student Nicole Howard works in a biosafety cabinet with the bacteria that cause tuberculosis, while Shabaana Khader looks on.

Some tuberculosis bacteria are harder to kill than others.

Patients infected with certain drug-resistant tuberculosis strains have to take multiple antibiotics continuously for up to two years to treat the infection. Research from Washington University now shows these resistant strains share a single mutation that weakens the host immune response.

An estimated 20 percent of previously treated tuberculosis cases are drug-resistant. Treating resistant strains often requires a combination of injectable antibiotics that can severely damage the liver.

Shabaana Khader, a professor of molecular microbiology at Wash U, said taking antibiotics for months at a time can be “a tough regime to keep up with.”

About two in three people who contract drug-resistant TB survive the illness — compared to more than 90 percent of people with drug-sensitive TB.

By sequencing the entire genome of multiple drug-resistant TB strains isolated from an outbreak in New York City in the 1990s, Khader and her research team were able to pinpoint a single mutation common across all the strains.

After finding this needle in a haystack, they decided to confirm their hunch by mutating a drug-sensitive TB strain.

Sure enough, it became drug-resistant.

But not only that, the mutated TB bacteria interacted differently with the mouse immune system, eliciting a slower, weaker immune response and essentially “disarming the burglar alarm” on the host cell.

“The drug-resistant bacteria were tricking the immune response into behaving differently,” Khader said. “They were triggering responses detrimental to the host, rather than the protective responses.”

This difference in immune response may be important when it comes to developing drug therapies to treat drug-resistant tuberculosis.

Specifically, Khader said, we might be able to use this information to try “targeting the host immune response to battle and control the infection better.”

The research team plans to repeat the study in human cells.

They also hope to investigate whether other other drug-resistant bacteria with this mutation, including strains of Staphylococcusand Enterococci, manipulate the host immune system in similar ways.

Follow Shahla on Twitter: @shahlafarzan

Shahla Farzan was a reporter at St. Louis Public Radio. Before becoming a journalist, Shahla spent six years studying native bees, eventually earning her PhD in ecology from the University of California-Davis. Her work for St. Louis Public Radio on drug overdoses in Missouri prisons won a 2020 Regional Edward R. Murrow Award.