Melting bacteria to decipher antibiotic resistance

E. coli bacteria colored in heat gradient. Credit: Aleksandra Krolik / EMBL

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.

Media Contact

Iris Kruijen
iris.kruijen@embl.de
49-622-138-78443

 @EMBL

http://www.embl.org 

Alle Nachrichten aus der Kategorie: Life Sciences

Articles and reports from the Life Sciences area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Zurück zur Startseite

Kommentare (0)

Schreib Kommentar

Neueste Beiträge

An artificial cell on a chip

Researchers at the University of Basel have developed a precisely controllable system for mimicking biochemical reaction cascades in cells. Using microfluidic technology, they produce miniature polymeric reaction containers equipped with…

Specific and rapid expansion of blood vessels

Nature Communications: KIT researchers identify a new mechanism to control endothelial cell size and arterial caliber – basis for better treatment of heart infarct and stroke. Upon a heart infarct…

Climate change drives plants to extinction in the Black Forest in Germany

Climate change is leaving its mark on the bog complexes of the German Black Forest. Due to rising temperatures and longer dry periods, two plant species have already gone extinct…

By continuing to use the site, you agree to the use of cookies. more information

The cookie settings on this website are set to "allow cookies" to give you the best browsing experience possible. If you continue to use this website without changing your cookie settings or you click "Accept" below then you are consenting to this.

Close