Research Indicates How TB Bacteria Remains Latent and Fights Immunity for Decades

Scientists from Memorial Sloan-Kettering Cancer Centre have identified a protein that helps TB bacteria resist immune response. This enables the bacteria to remain latent in the body for decades.

They hope that the new discovery may lead to new drugs to eliminate those strains of mycobacterium tuberculosis that have grown resistant to therapies currently available.

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Tuberculosis, caused by Mycobacterium tuberculosis, primarily affects the lung. It may spread to other organs.

"Tuberculosis can resist the host immune system and remain latent for decades," said Michael Glickman, of the Memorial Sloan-Kettering Cancer Centre.

"To do so, the mycobacterium responsible must resist an arsenal of DNA-damaging mutagens produced within the macrophage, the immune cell in which it lives.

"It's incompletely understood how it can do that. We've identified one such mechanism," he added.

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According to the researchers, secret to TB's success is a protein called CarD.

"The mycobacterium tailors its translational machinery in response to stress within the host and we have identified CarD as a critical mediator of this response" said Glickman.

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The study showed that loss of CarD is fatal to M. tuberculosis living in cell culture.

CarD depletion leaves the pathogen sensitive to killing by oxidative stress, starvation, and DNA damage as it fails to cut its transcription of rRNA.

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Glickman said that they were able to show in infected mice that the mycobacterium depends on CarD not just when it is in its early, most active phase of growth, but also later in the course of infection.

He added that drugs that target CarD's interaction with RNA polymerase could, therefore, lead to sorely needed, new TB drugs.

The study has been published in the journal Cell, a Cell Press publication.

Source-ANI
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