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Tuberculosis bacterium has a tricky defence

by Bruno Van de Casteele

December 2, 2012

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Donate "Know your enemy"seems also the motto for theBelgian researchers from the Free University of Brussels. They have uncovered one moredefensemechanism of the Tuberculosis bacterium, potentially finding another line of attack against this disease.

The bacterium responsible for tuberculosis, Mycobacterium tuberculosis, can resist very well our macrophages, our white blood cells that "eat" and digest intruders. One of the methods to digest is via reactive oxygen molecules. These are especially effective against proteins with sulphur-containing components by oxidizing the sulphur chains. Macrophages, after engulfing the bacterium, apply the oxygen to prevent these proteins from folding and thus from replicating. The threat is then, in theory, contained and the macrophages disassemble the bacterium to remove it definitely from our body.

The tuberculosis bacterium however defends its proteins by applying the mycothiol molecule on them. Consider this a sort of protective blanket. As it also prevents folding, it needs to be removed after the attack subsides. Until now it was not clear how this removal exactly happened.

The team around Joris Messens has now found this happens via another protein, mycoredoxin-1. They published their researchin Molecular Microbiology. The protein in questions searches for and removes the mycothiol molecule, thereby re-enabling these proteins. Not only do the proteins survive, they are still as good as before and continue to make their human host ill.

In some press articles this was touted as "the missing link" or "defense finally cracked". It is an impressive discovery, but don't get your hopes up too soon. It is good that we now know more about one of the defense mechanisms. The next step now is to look for ways to desactivate mycoredoxin-1. This will ensure that the proteins stay under their protective layer, and be unable to fold.

But even if such a method is immediately found (in my opinion probably not very likely), it then still has to pass all tests in animals and humans, so we're at least ten years away from having this in our pharmacies. That is, when there are no nasty side-effects and it can be easily put into production. On top of that, the tuberculosis bacterium has multiple lines of defense (Wikipedia lists a couple of others, with references).

It's a nice step forward, and great to see such research done, but it's only a part of the ongoing struggle to master this disease.

by Bruno Van de Casteele

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