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Tuberculosis hides in bone marrow stem cells

4 February 2013
Appeared in BioNews 691

The bacteria that cause tuberculosis (TB) evade immune cells and drug treatments by hiding in bone marrow stem cells, according to research.

In the first part of their study, scientists isolated live bacteria from bone marrow stem cells of mice with a 'latent' form of TB where the infection is not accompanied by disease symptoms. Then, in the clinical part of the study, nine people who had been successfully treated for TB and showed no signs of the disease were shown to have bacterial DNA in their stem cells. Viable TB bacteria were recovered from two of these patients.

This hiding tactic, which the researchers call the 'wolf in stem cell clothing', may help to explain why it is so difficult to treat latent TB. Between five and ten percent of patients with latent TB will go on to develop the active form of the disease.

Professor Dean Felsher of Stanford University School of Medicine, a senior author of the study, said: 'Self-renewing stem cells like these in the bone marrow have properties - such as natural drug resistance, infrequent division and a privileged immune status - that make them immune to many types of treatment. Now it turns out that this ancient organism, Mycobacterium tuberculosis, figured out a long time ago that, for the same reasons, these cells are ideal hosts to invade and in which to hide'.

Latent TB affects over two billion people worldwide, although most will be unaware that they have been infected. The active form of TB, which causes devastating lung disease, led to an estimated 1.4 million deaths in 2011. Drugs effective against TB have been available for 50 years but TB often recurs years after the initial treatment.

The President of the Australian Medical Association Dr Steve Hambleton, who was not part of the study, told ABC News that this was the first time that living TB had been found in patients after six months of treatment. He said: 'It may actually help us in working out why recurrences occur. We may actually be able to stop them recurring. It is a huge global health problem'.

The stem cells most affected were a sub-population known as mesenchymal stem cells, which are present in bone marrow and can migrate to the lungs where TB thrives. Professor Felsher noted that these cells had 'never been implicated as a host for tuberculosis'.

Mesenchymal stem cells may yet become a target for drug therapies against TB but any commercially available treatment would likely be decades away.

The research was published in the journal Science Translational Medicine.

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