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So that's where tuberculosis hides

Thu, 31st Jan 2013

Chris Smith

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In a move that will make tuberculosis (TB) easier to treat, scientists have discovered a hidden hang-out used by the bacterium to evade immune capture or destruction by Mycobacterium Tuberculosisantibiotics.

Writing in Science Translational Medicine, Antonia Campos-Neto, from the Forsyth Institute in Massachusetts, and his colleagues have flushed out a previously unknown hiding place where TB can lurk beyond the reach of drugs or the immune system.

Using experimental mice, the team have discovered that TB bacteria (Mycobacterium tuberculosis) can get inside the stem cells that make up the bone marrow and lurk, in an inactive state, invisible to the immune system.

Bone marrow stem cells are an ideal target because they divide, rather than die, so the TB bacteria always have a home, the cells reside in a so-called immune privileged site, where the immune system is held in check, and these cells produce a molecule called an ABCG2 efflux pump, which rapidly removes anti-TB drugs from the cells.

In tests, the team were able to show that TB could be successfully cultured many months later after mice were infected via the airborne route with TB.

Even more convincing was the finding that the bug could also be grown from bone marrow samples obtained from previously-treated human TB cases, who were otherwise regarded as cured.

The good news is that the infected stem cells that the team have identified carry a specific marker on their surfaces called CD271. So now a targeted therapy can be developed to ensure the bacteria are flushed out from these cells too.

This cannot come a moment too soon: official figures show that over 2 billion people worldwide are currently TB infected...

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Very interesting.
I wonder how many other microorganisms use a similar method to enter a dormant phase.

CD271is apparently a natural marker on these marrow cells, so one wouldn't want to treat with an anti- CD271 antibody, unless one was also planning a marrow transplant.  Perhaps one could do an autologous marrow transplant with cultured uninfected cells.  But, such a therapy would be expensive, and not without risk.

However, perhaps one could temporarily block the ABCG2 efflux pump, allowing greater intracellular drug concentrations for the TB medications, as well as other medications. CliffordK, Thu, 31st Jan 2013

Does this mean that the bacteria always live in the bone marrow cells? heraclesblack, Fri, 1st Feb 2013

When the body has trouble completely killing off a bacteria, it will wall it off, in graulomas in the lung or cysts.

When the body has trouble completely killing off a bacteria, it will wall it off, in graulomas in the lung or cysts in other tissues. This happens to some parasites as well. Soldiers who fought in WW I and II sometimes had infections caught over seas like Schistosoma reactivating 50 years later when their immune system weakened. cheryl j, Sun, 3rd Feb 2013

It won't kill the TB if it's quiescent inside a bone marrow stem cell though, will it! That's the whole point of this discovery being so signficant... chris, Tue, 5th Feb 2013

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