EMBL scientists investigate how bacteria melt to study their reaction to drugs
With antibiotic resistance spreading worldwide, there is a strong need for new technologies to study bacteria. EMBL researchers have adapted an existing technique to study the melting behaviour of proteins so that it can be used for the study of bacteria. Molecular Systems Biology published their results - allowing researchers worldwide to start using the technique - on July 6.
Thermal proteome profiling (TPP) was developed in 2014 (Savitski et al., Science 2014) and enables scientists to compare the melting behavior of all proteins in a cell or organism before and after a perturbation, such as the administration of a drug.
By adapting TPP to bacteria, it can now be used to study the activity and architecture of most proteins in a bacterial cell while it's alive. André Mateus, a postdoc working in the Savitski and Typas groups at EMBL, led the study.
Bacteria taking the heat
While human bodies cease to function at temperatures above 42°C, E. coli bacteria still grow regularly up to 45°C. "We discovered that proteins in the middle of a bacterial cell are less tolerant to heat than those at the cell surface," says Mikhail Savitski. "Surprisingly, a protein's location is more predictive for its melting behavior than which other proteins it interacts with."
With TPP, researchers can also investigate the effects of drugs on bacteria. Protein-drug interactions typically increase the proteins' heat tolerance, resulting in higher melting points. Therefore, comparing the heat tolerance of drug-treated and untreated bacterial cells helps to identify targets of antimicrobial drugs, but also to decipher how the bacterial cell succumbs to the drug or tries to bypass its action.
Drug resistance mechanisms
"In one particular case, we were able to elucidate a novel drug resistance mechanism," says André Mateus. "Cells use proteins to pump antibiotics out of the cell. After genetically removing one such efflux pump from their chromosome, bacteria became more sensitive to many drugs, but curiously more resistant to one specific antibiotic called aztreonam. Using TPP, we found that this was due to dramatically reduced levels of a specific porin - a protein that acts as a pore - used by aztreonam to enter the cell."
Compared to other techniques, TPP allows scientists to investigate the effects of perturbations on thousands of individual proteins in a short timeframe. Most of the obtained insights - like the changes in the activity of proteins in vivo - would be impossible with other conventional techniques and for so many proteins simultaneously, showing TPP's potential to study bacteria in detail.
Iris Kruijen | EurekAlert!
If Machines Could Smell ...
19.07.2019 | Fraunhofer-Institut für Produktionstechnik und Automatisierung IPA
Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University
Adjusting the thermal conductivity of materials is one of the challenges nanoscience is currently facing. Together with colleagues from the Netherlands and Spain, researchers from the University of Basel have shown that the atomic vibrations that determine heat generation in nanowires can be controlled through the arrangement of atoms alone. The scientists will publish the results shortly in the journal Nano Letters.
In the electronics and computer industry, components are becoming ever smaller and more powerful. However, there are problems with the heat generation. It is...
Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.
Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...
Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.
Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...
For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.
Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...
An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".
The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...
24.06.2019 | Event News
29.04.2019 | Event News
17.04.2019 | Event News
19.07.2019 | Physics and Astronomy
19.07.2019 | Physics and Astronomy
19.07.2019 | Earth Sciences