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Fighting bacteria with viruses.

Viruses called bacteriophages may help destroy the bacterium Clostridium difficile, which has resistance to antibiotics. Recent research should help engineer effective, specific bacteriophages targeting a wide range of bacteria related to human health, agriculture and food.

C. difficile infections, which can be fatal, are currently very difficult to treat, as the bacterium is unresponsive to many antibiotics. One possible solution would be to 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, a bacterial cell can no longer withstand its own internal pressure, and it explodes. The newly formed viruses burst out to find new hosts, and the bacterium is destroyed in the process.

Investigators first need to know exactly how these viruses destroy bacterial cell walls. Researchers are aware of the viruses' demolition machines--endolysins--but just how these enzymes are activated was unclear until now.

Scientists at the UK's Institute of Food Research examined how engineering mutations in endolysins, which are hydrolytic enzymes, affected their ability to tear down the bacterial cell wall. These enzymes appear to switch from a tense, elongated shape, in which a pair of endolysins is joined together, to a relaxed state in which the two endolysins lay side-by-side. The switch from one conformation to the other releases the active enzyme, which then begins to degrade the cell wall.

Researchers compared the structures of endolysins from two different bacteriophages, which target different kinds of Clostridium. Remarkably, the scientists found that the two endolysins share this common activation mechanism, despite being from different species of Clostridium.

This is an indicator that the transition between tense and relaxed states is likely a widespread tactic, and could therefore be used to turn other viruses into allies in the fight against other antibiotic-resistant bacteria. Gaining insights into the mode of action of phage endolysins will help scientists design improved phage-derived therapies that are needed to address the current problem of antibiotic-resistant bacteria.

Further information. Arjan Narbad, Institute of Food Research, Norwich Research Park, Colney, Norwich NR4 7UA, UK; phone: +44 1603 255000; fax: +44 1603 507723; email:

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Publication:Emerging Food R&D Report
Date:Jun 1, 2016
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