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 firstname.lastname@example.org http://s.embl.org/press
Sonia Furtado Neves | EMBL Press
A new potential biomarker for cancer imaging
05.02.2016 | Universiti Putra Malaysia (UPM)
NIH researchers identify striking genomic signature shared by 5 types of cancer
05.02.2016 | NIH/National Human Genome Research Institute
Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...
Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.
Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...
NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.
Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...
In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.
In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...
The ‘Internet of Things’ is growing rapidly. Mobile phones, washing machines and the milk bottle in the fridge: the idea is that minicomputers connected to these will be able to process information, receive and send data. This requires electrical power. Transistors that are capable of switching information with a single electron use far less power than field effect transistors that are commonly used in computers. However, these innovative electronic switches do not yet work at room temperature. Scientists working on the new EU research project ‘Ions4Set’ intend to change this. The program will be launched on February 1. It is coordinated by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).
“Billions of tiny computers will in future communicate with each other via the Internet or locally. Yet power consumption currently remains a great obstacle”,...
02.02.2016 | Event News
26.01.2016 | Event News
26.01.2016 | Event News
05.02.2016 | Life Sciences
05.02.2016 | Materials Sciences
05.02.2016 | Physics and Astronomy