Why certain TB bacteria can be lethal

Although drug-resistant tuberculosis is so deadly in part because some first-choice antibiotics fail to kill TB bacteria, the TB bacteria may also be undermining the body's ability to defend itself, a study published in Nature Microbiology found.

Researchers at Washington University School of Medicine in St. Louis found the same mutation that makes TB bacteria resist a first-line drug also draws out a potentially weaker immune response in mice.

"As the bacteria become drug-resistant, they change physiologically and trick the immune system to behave differently," said senior study author Shabaana Khader, PhD. "If we're going to fight TB bacteria effectively, we're going to have to understand what the drug-resistant bacteria are doing to the immune system to elicit protection."

The researchers looked at immune responses in mice infected with Mycobacterium tuberculosis, the bacteria that cause TB. They compared a strain resistant to all first- and many second-line antibiotics with a drug-sensitive TB strain.

The mice's immune systems fought the sensitive bacteria by releasing a powerful immune molecule and increasing their immune cells' ability to burn sugar, which is critical to attack the TB bacteria.

When infected with the drug-resistant strain, however, the mice's immune cells did not burn more sugar, and they failed to produce much of the powerful immune molecule. They instead released a different immune molecule that is linked to a weak and potentially detrimental immune response to TB.

"People always thought that development of drug resistance just meant that there's a change in how bacteria respond to antibiotics," Dr. Khader said. "But this shows that the whole immune environment is changing in ways that we haven't been fully aware of."

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