Bacteriophages could be new tool to fight C. diff
infections in hospitals
4 August 2014
A class of viruses called bacteriophages can infect and destroy
the bacterium Clostridium difficile (C. diff),
according to research at the European Molecular Biology Laboratory
(EMBL) in Hamburg, Germany, and published in PLOS Pathogens.
C. diff is becoming a serious problem in hospital
patients due to its resistance to antibiotics and the new findings
could help bring about a new way of fighting this and other
Bacteriophages are viruses that infect only bacteria and hijack
the bacterium’s DNA-reading machinery to create 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.
Electron microscopy image of the bacteriophages.
Credit: Kathryn Cross/IFR.
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
bacteriophage uses enzymes called endolysins to destroy the cell
walls, but just how these enzymes are activated was unclear until
The analysed endolysins are activated by
from a tensed, stretched state (left) to a relaxed
Credit: EMBL/Rob Meijers.
“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
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
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.
Dunne, M et al. The CD27L and CTP1L endolysins targeting
Clostridia contain a built-in trigger and release factor. PLoS
Pathogens, 24 July 2014.