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
Killer sea snail a target for new drugs
07.07.2015 | University of Queensland
First images of dolphin brain circuitry hint at how they sense sound
07.07.2015 | Emory Health Sciences
When a duck paddles across a pond or a supersonic plane flies through the sky, it leaves a wake in its path. Wakes occur whenever something is traveling...
Researchers explore ultrafast control of magnetism across interfaces: A new study discovers how the sudden excitation of lattice vibrations in a crystal can trigger a change of the magnetic properties of an atomically-thin layer that lies on its surface.
A research team, led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter at CFEL in Hamburg, the University of Oxford, and the...
Wind turbines could be installed under some of the biggest bridges on the road network to produce electricity. So it is confirmed by calculations carried out by a European researchers team, that have taken a viaduct in the Canary Islands as a reference. This concept could be applied in heavily built-up territories or natural areas with new constructions limitations.
The Juncal Viaduct, in Gran Canaria, has served as a reference for Spanish and British researchers to verify that the wind blowing between the pillars on this...
New technique combines electron microscopy and synchrotron X-rays to track chemical reactions under real operating conditions
A new technique pioneered at the U.S. Department of Energy's Brookhaven National Laboratory reveals atomic-scale changes during catalytic reactions in real...
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.
Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...
25.06.2015 | Event News
16.06.2015 | Event News
11.06.2015 | Event News
07.07.2015 | Physics and Astronomy
07.07.2015 | Earth Sciences
07.07.2015 | Physics and Astronomy