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A centuries-old herbal Chinese medicine, used to effectively treat malaria, may help fight tuberculosis and slow the evolution of drug resistance, scientists have found. In a study led by Robert Abramovitch, from the Michigan State University in the US, the ancient remedy artemisinin stopped the ability of TB-causing bacteria, known as Mycobacterium tuberculosis, to become dormant.
This stage of the disease often makes the use of antibiotics ineffective. “When TB bacteria are dormant, they become highly tolerant to antibiotics,” Abramovitch said. “Blocking dormancy makes the TB bacteria more sensitive to these drugs and could shorten treatment times,” he said.
Mycobacterium tuberculosis, or Mtb, needs oxygen to thrive in the body. The immune system starves this bacterium of oxygen to control the infection. Abramovitch and his team found that artemisinin attacks a molecule called heme, which is found in the Mtb oxygen sensor.
By disrupting this sensor and essentially turning it off, the artemisinin stopped the disease’s ability to sense how much oxygen it was getting. “When the Mtb is starved of oxygen, it goes into a dormant state, which protects it from the stress of low-oxygen environments,” Abramovitch said. “If Mtb can’t sense low oxygen, then it can’t become dormant and will die,” he said.
Abramovitch indicated that dormant TB can remain inactive for decades in the body. However, if the immune system weakens at some point, it can wake back up and spread. Whether it wakes up or stays ‘asleep’ though, he said TB can take up to six months to treat and is one of the main reasons the disease is so difficult to control. “Patients often don’t stick to the treatment regimen because of the length of time it takes to cure the disease,” he said.
“Incomplete therapy plays an important role in the evolution and spread of multi-drug resistant TB strains,” he said. The research could be key to shortening the course of therapy because it can clear out the dormant, hard-to-kill bacteria. This may lead to improving patient outcomes and slowing the evolution of drug-resistant TB.
After screening 540,000 different compounds, Abramovitch also found five other possible chemical inhibitors that target the Mtb oxygen sensor in various ways and could be effective in treatment as well. “TB is a global problem that requires new tools to slow its spread and overcome drug resistance. This new method of targeting dormant bacteria is exciting because it shows us a new way to kill it,” said Abramovitch.
The study was published in the journal Nature Chemical Biology.
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