After years of work, VIB researchers at the Vrije Universiteit Brussel (VUB) were able to determine the structure and operating mechanism of the proteins involved.
This clears the road for finding ways to set the clock on this internal time bomb and, hopefully, in the process developing a new class of antibiotics. The research was accepted for publication by top journal Molecular Cell, with congratulations from the editorial board.
It's in the genes
For years, Nathalie De Jonge, Remy Loris and their colleagues of the VIB Department of Molecular and Cellular Interactions at VUB, have applied their relentless dedication to the study of the precise structure and function of the toxin-antitoxin complex, a system that had not been the focus of much interest in the past. Only in the last couple of years the rest of the scientific world come to realize its importance and as a result the number of papers in this field has exploded.
All living creatures, people as well as bacteria, store their genetic information in the same way, i.e. in the DNA. Every human cell contains 46 neatly folded DNA strands that together measure two meters, while bacteria have to make do with around one millimetre of DNA. A piece of DNA containing the recipe for one characteristic, such as "how to make citric acid" or "how to make hair curl," is called a gene. Humans have several tens of thousands of genes.
Toxin and antitoxin
If your genetic information becomes damaged, you have a good chance of becoming ill or even dying. This is also true for bacteria, which over time developed a handy way of providing extra protection to important genes – the toxin-antitoxin (T-A) system. These T-A genes are tucked in near the genes to be protected. T-A genes contain instructions for both a toxin and its antitoxin. As long as the cell is producing both, all is well. However, if for some reason the piece of DNA where the T-A gene is located gets damaged or lost, the production of toxin and antitoxin comes to a halt and a time bomb starts ticking. Because the toxin is more stable than the antitoxin, it is broken down more slowly by the cell's clean-up mechanisms. Once the antitoxin is all gone, there is still enough toxin left to kill the bacterium. The upshot for the species is that bacteria that loses their T-A gene – and probably have sustained damage to the important genes just next to it – can no longer reproduce.
Our best-known intestinal residents, Escherichia coli bacteria, more commonly known as E.coli, have such a T-A system in five different locations in their DNA, while Mycobacterium tuberculosis bacteria even have them in 60 locations.
A difficult feat
The T-A mechanism has been known for a while, but nobody clearly understood the workings of the proteins carrying out the instructions of the T-A gene. The VIB researchers clarified in detail both the appearance of the toxin and antitoxin, the mechanism of their interaction and the forms they take while in action – a difficult feat to pull off, requiring the simultaneous use of a whole range of different technologies. One of the difficulties for instance lay in the fact that part of the antitoxin lacks a fixed structure. This formlessness keeps it from being brought into view.
Now that we finally know how the time bomb functions (or more exactly, one of the time bombs, as there are several closely related T-A systems), biomedical scientists can start looking for substances to start the time bomb of pathogens ticking, i.e. substances that imitate the toxin protein, block the antitoxin protein, or disrupt the interaction between the toxin and antitoxin. In time, a new class of antibiotics might come out of it – though Nature mostly has a countermove up its sleeve against any move scientists do.
Pieter Van Dooren | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences