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!
What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society
Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy