Fighting bacteria—with viruses

Jul 24, 2014

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 – 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 , 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 .

Explore further: Study provides new perspectives on the current Clostridium difficile epidemic

add to favorites email to friend print save as pdf

Related Stories

Virus Enzymes Could Promote Human, Animal Health

Aug 31, 2009

(PhysOrg.com) -- Could viruses be good for you? Scientists with the Agricultural Research Service (ARS) have shown that enzymes from bacteria-infecting viruses known as phages could have beneficial applications ...

Bacteriophages battle superbugs

Jul 18, 2013

IFR microbiologists are reinvigorating a way of battling C. difficile infections that they hope will help overcome the growing problem of antibiotic resistant superbugs in hospitals.

Recommended for you

YEATS protein potential therapeutic target for cancer

Oct 23, 2014

Federal Express and UPS are no match for the human body when it comes to distribution. There exists in cancer biology an impressive packaging and delivery system that influences whether your body will develop cancer or not.

Precise and programmable biological circuits

Oct 23, 2014

A team led by ETH professor Yaakov Benenson has developed several new components for biological circuits. These components are key building blocks for constructing precisely functioning and programmable bio-computers.

User comments : 0