Tuberculosis bacteria's defence mechanism discovered — opens way for
22 November 2012
A team of Flemish biologists have discovered that the
tuberculosis bacterium has an ingenious defence mechanism against
oxidation, the system used by the body to attack invading bacteria. This
finding is important in the search for a treatment for the disease that
infects 9.4 million people annually and kills 1.7 million people.
Joris Messens, leader of the research team from VIB and Vrije
Universiteit Brussel, said, “We have discovered how Mycobacterium
survives the oxygen stress in our body, namely with the aid of the
protein mycoredoxin-1. This opens up a whole new field of research
into the role of this protein during a tuberculosis infection. A
better understanding of this mechanism will enable us to combat this
bacterium more selectively.”
Oxygen, a necessary evil
Oxygen is essential for the respiration of nearly all cells. They
use this gas to burn sugars in order to produce energy. However,
oxygen is also very aggressive and can seriously affect proteins —
the building blocks of the cell — in a manner similar to rust or
oxidation of iron.
Our immune system uses reactive oxygen molecules in the defence
against intruders, for example against Mycobacterium bacteria.
Proteins are particularly sensitive to the effects of oxygen
(oxidation). Proteins with sulphur-containing components are
particularly sensitive and become inactive with oxidation. Following
damage by oxygen, Mycobacterium places the mycothiol molecule on
such proteins. After a period of oxygen stress this molecule has to
be removed again for the proper functioning of the protein. It was
not known how this happened, until now.
Protection and recovery
Joris Messens and his team have discovered that Mycobacterium
tuberculosis protects sulphur-containing proteins in a unique
way and actively repairs these proteins once the oxygen stress
disappears. They discovered the protein mycoredoxin-1, which forms
the basis of this ingenious repair mechanism. The scientists
analysed the protein structure and the function of the protein and
found that mycoredoxin-1 selectively removes mycothiol from affected
sulphur-containing proteins and thereby ensures the activation of
Joris Messens said: “We could combat tuberculosis more
effectively by searching for components that disable mycoredoxin-1.
The bacterium would not be able to recover as quickly from an oxygen
attack by our immune system.”
Van Laer et al. (2012) Mycoredoxin-1 is one of the
missing links in the oxidative stress defense mechanism of
Mycobacteria. Mol Microbiol 86: 787-804.
Antelmann, H. and Hamilton, C. J. (2012) Bacterial mechanisms of
reversible protein S-thiolation: structural and mechanistic insights
into mycoredoxins. Mol Microbiol. 86: 759-764