The potentially fatal Clostridium difficile bacterium is a serious problem in hospitals due to its resistance to antibiotics. However, a team of scientists from the European Molecular Biology Laboratory in Hamburg, Germany, may have found a new way to treat these difficult bacteria - by using viruses to "eat" them.

Viruses called bacteriophages infect only bacteria, using the bacteria's own DNA-reading machinery to duplicate themselves and destroy the bacteria's cell walls. Breaking down these walls causes the bacteria to explode, allowing the bacteriophages to burst out and find new bacteria to attack.

Rob Meijers, from the European Molecular Biology Laboratory (EMBL), led the research and believes that their study could have wide-reaching implications:

"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."

The problem with C. diff

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The bacteriophage endolysins switch conformation, from a tense, elongated shape (left) to a relaxed state where two endolysins sit side by sides (right).
Image credit: EMBL/Rob Meijers

Every year, over half a million people become ill due to C. diff, experiencing symptoms including watery diarrhea, abdominal cramping, fever, dehydration and kidney failure. Once established, C. diff bacteria attack the lining of the intestine with toxins.


One of the most problematic aspects of C. diff is that antibiotics can lead to the bacteria establishing themselves within the intestine.

If an antibiotic is taken to treat one kind of infection, it can destroy some of the helpful bacteria that live in the intestine, leaving it without enough bacteria to defend it against C. diff.

C. diff is commonly treated with further antibiotics but is particularly unresponsive to a large number of them. With subsequent recurrences of C. diff infection, the effectiveness of antibiotic therapy is reduced, and the risk of recurrence is increased if the person is taking other antibiotics for another condition.

The use of bacteriophages could avoid these problems. In order to use them, scientists have needed to find out how precisely the viruses destroy cell walls. The parts of the virus that accomplish this, the endolysins, were already known, but only now have scientists discovered how they are activated.


Co-author Matthew Dunne explains how:





"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. The switch from one conformation to the other releases the active enzyme, which then begins to degrade the cell wall."

Switching from 'standby' to 'attack' mode

The authors of the study, published in PLOS Pathogens, were able to discover the switch from one conformation to the other by working out the 3D structure of the endolysins using X-ray crystallography and small angle X-ray scattering.

The scientists then compared the endolysin structures of two bacteriophages that target different species of Clostridium bacteria; one that targets C. diff and one that targets a Clostridium strain that is found in fermenting cheese.

The activation mechanism was found to be shared by both the species of Clostridium-targeting bacteriophages, leading the team to conclude that this is likely to be a common feature and could be harnessed in order to use other viruses to attack antibiotic-resistant bacteria.

If the discovery of this structural switch enables scientists to engineer viruses as an alternative to antibiotics, then it could spell the end for health care-associated infections such as C. diff, which remains at historically high levels and is responsible for 14,000 deaths linked to diarrhea each year.

Earlier in the year, Medical News Today reported on a study that found that a quarter of health care workers carry C. diff spores on their hands, highlighting a possible route through which the bacteria spreads in hospitals.