CnoX, a bacterial shield against the immune system

(Translated from UCLouvain press release)

23/06/2018

A major discovery at UCL in the fight against bacterial infections. Jean-François Collet and his team have discovered a new protein, CnoX, which plays a major role in the defense of bacteria against our immune system. Thanks to this discovery, the UCL researchers will be able to develop a system of neutralization of this protein and thus weaken the defense of bacteria against attacks by the immune system. This will contribute to the development of new molecules to fight against antibiotic-resistant bacteria. The research results have just been published in the prestigious scientific journal Molecular Cell.

In everyday life, we use bleach when we want to attack bacteria, for example to clean the kitchen or bathroom. The human body acts the same way! To fight against bacteria, the cells of our immune system produce hypochlorite, an oxidizing molecule that is also found in bleach. Hypochlorite attacks bacteria by oxidizing and unfolding their proteins. The problem? Bacteria defend themselves and infections persist. Jean-François Collet and his team, at the de Duve Institute of UCL, have been looking for years for new ways to strengthen our arsenal of antibacterial defense mechanisms.

The work of Camille Goemans, at the time a PhD student at the UCL’s de Duve Institute (and now a postdoc at the European Molecular Biology Laboratory in Germany), allowed a major breakthrough in this research. The novelty? The discovery of the bacterial protein CnoX. It’s action? Instead of being unfolded by hypochlorite (bleach), as are other bacterial proteins, CnoX (a chaperone protein) gets activated, protects bacteria from oxidation and helps damaged proteins to refold correctly. Once the attack is over, CnoX transfers its substrates to chaperones that are able to use cellular energy to correctly refold the hypochlorite-damaged proteins. Another revelation from the UCL researchers: CnoX, produced by a large number of bacteria, is the first protein identified to have both a chaperone activity and a protective activity against oxidation. The protein is essential for the survival of bacteria such as Escherichia coli in the presence of bleach. Clearly, CnoX allows bacteria to survive the attacks of our immune system and thus infections to persist.

The emergence of antibiotic-resistant bacteria is a threat to humans and medicine as we know it today. Unfortunately, it is not fanciful to think that epidemics like those depopulating entire cities not so long ago can reappear. It is therefore urgent to find new ways and new targets to strengthen our defense arsenal. Because CnoX helps bacteria to withstand the cells of our immune system, it could be an interesting target for the development of new antibacterial molecules and thus contribute to strengthening the well-being of humanity.

These UCL research results have just been published in the prestigious scientific journal Molecular Cell. A feat that indicates the importance of this research, since it is only the second UCL article published in this journal in 20 years.

Article describing this research

Molecular Cell (2018), 70:614–627.e7

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