Study reveals promising information for developing an alternative to antibiotics
Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its resistance to antibiotics. The study, by scientists at the European Molecular Biology Laboratory (EMBL) in Hamburg, Germany, could help bring about a new way of fighting this and other bacteria.
“Our findings will help us to engineer effective, specific bacteriophages, not just for C. diff infections, but for a wide range of bacteria related to human health, agriculture and the food industry,” says Rob Meijers from EMBL, who led the work. C. diff infections, which can be fatal, are currently very difficult to treat, as the bacterium is particularly unresponsive to many antibiotics.
A possible solution would be not to use antibiotics, but instead employ bacteriophages – viruses which infect only bacteria. Scientists know that these viruses hijack a bacterium’s DNA-reading machinery and use it to create many new bacteriophages. These then start demolishing the bacterium’s cell wall. Once its wall begins to break down, the bacterial cell can no longer withstand its own internal pressure and explodes.
The newly formed viruses burst out to find new hosts and the bacterium is destroyed in the process. To harness the power of bacteriophages and develop effective therapies against bacteria like C.diff, scientists need to know exactly how these viruses destroy bacterial cell walls. The viruses’ demolition machines, endolysins, are known, but just how these enzymes are activated was unclear – until now.
“These enzymes appear to switch from a tense, elongated shape, where a pair of endolysins are joined together, to a relaxed state where the two endolysins lie side-by-side,” explains Matthew Dunne who carried out the work. “The switch from one conformation to the other releases the active enzyme, which then begins to degrade the cell wall.”
Meijers and collaborators discovered the switch from ‘standby’ to ‘demolition’ mode by determining endolysins’ 3-dimensional structure, using X-ray crystallography and small angle X-ray scattering (SAXS) at the Deutsches Elektronen-Synchrotron (DESY). They compared the structures of endolysins from two different bacteriophages, which target different kinds of Clostridium bacteria: one infects C. diff, the other destroys a Clostridium species that causes defects in fermenting cheese.
Remarkably, the scientists found that the two endolysins share this common activation mechanism, despite being taken from different species of Clostridium. This, the team concludes, is an indicator that the switch between tense and relaxed enzymes is likely a widespread tactic, and could therefore be used to turn other viruses into allies in the fight against other antibiotic-resistant bacteria.
The work was performed in collaboration with Arjan Narbad’s lab at the Institute of Food Research in Norwich, UK, who tested how engineering mutations in the endolysins affected their ability to tear down the bacterial cell wall.
To be published online in PLoS Pathogens on 24 July 2014: http://dx.plos.org/10.1371/journal.ppat.1004228.
For images and for more information please visit: www.embl.org/downloads/2014/140724_Hamburg (username = press, password = images4u)
Policy regarding use EMBL press and picture releases including photographs, graphics and videos are copyrighted by EMBL. They may be freely reprinted and distributed for non-commercial use via print, broadcast and electronic media, provided that proper attribution to authors, photographers and designers is made.
Sonia Furtado Neves EMBL Press Officer & Deputy Head of Communications Meyerhofstr. 1, 69117 Heidelberg, Germany Tel.: +49 (0)6221 387 8263 Fax: +49 (0)6221 387 8525 email@example.com http://s.embl.org/press
Sonia Furtado Neves | EMBL Press
New technology helps ID aggressive early breast cancer
01.07.2016 | University of Michigan Health System
In times of great famine, microalgae digest themselves
01.07.2016 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung
Densified regions with drastically reduced internal motion either act as crystal precursors or cluster and frustrate all further dynamics
Glasses are neither fluids nor crystals. They are amorphous solids and one of the big puzzles in condensed matter physics. For decades, the question of how...
Since the completion of the human genome an important goal has been to elucidate the function of the now known proteins: a new molecular method enables the investigation of the function for thousands of proteins in parallel. Applying this new method, an international team of researchers with leading participation of the Technical University of Munich (TUM) was able to identify hundreds of previously unknown interactions among proteins.
The human genome and those of most common crops have been decoded for many years. Soon it will be possible to sequence your personal genome for less than 1000...
3D printing revolutionized the manufacturing of complex shapes in the last few years. Using additive depositing of materials, where individual dots or lines...
R2D2, a joint project to analyze and development high-TRL processes and technologies for manufacture of flexible organic light-emitting diodes (OLEDs) funded by the German Federal Ministry of Education and Research (BMBF) has been successfully completed.
In contrast to point light sources like LEDs made of inorganic semiconductor crystals, organic light-emitting diodes (OLEDs) are light-emitting surfaces. Their...
High resolution rotational spectroscopy reveals an unprecedented number of conformations of an odorant molecule – a new world record!
In a recent publication in the journal Physical Chemistry Chemical Physics, researchers from the Max Planck Institute for the Structure and Dynamics of Matter...
30.06.2016 | Event News
28.06.2016 | Event News
09.06.2016 | Event News
01.07.2016 | Physics and Astronomy
01.07.2016 | Earth Sciences
01.07.2016 | Medical Engineering