Scientists develop alternative to antibiotics

Researchers at the European Molecular Biology Laboratory (EMBL) in Germany have revealed how viruses known as bacteriophages are capable of destroying the bacterium Clostridium difficile (C. DIFF), which is becoming an increasing problem in hospitals and healthcare institutes, due to its resistance to antibiotics.

The research was published today in the journal PLOS Pathogens.

The scientists suggest these new findings could be used to develop alternatives to fighting C. DIFF and other types of bacteria - effectively reducing our reliance on antibiotic treatments.

“The endolysins will only target the pathogenic bacterial strain, which is a great advantage over the use of antibiotics

EMBL researcher Rob Meijers

“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,” said Rob Meijers from EMBL, who led the research.

The issue with C. DIFF infections is that they are notoriously difficult to treat, and antibiotics often struggle to gain any form of response when deployed against this type of bacterium.

The EMBL team, therefore, has employed the use of bacteriophages - viruses which only infect bacteria, not the body.

Once viruses hijack a bacterium’s DNA-reading machinery, newly created bacteriophages set about destroying the bacterium’s cell wall, and once the wall breaks down, the bacterial cell can no longer withstand its own internal pressure, causing it to explode.

The newly formed viruses navigate the body to find new hosts and the bacterium is destroyed in the process, the researchers claim.

Until now, it was unclear how the viruses’ demolition machines, endolysins, were activated.

“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,” said Matthew Dunne who helped carry out the study.

“The switch from one conformation to the other releases the active enzyme, which then begins to degrade the cell wall,” he said.

The EMBL team discovered the switch from ’standby’ to ’demolition’ mode by determining endolysins’ three-dimensional structure, using X-ray crystallography and small angle X-ray scattering (SAXS) at the Deutsches Elektronen-Synchrotron (DESY).

Meijers suggests 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.

Speaking with Laboratorytalk about the research, Meijers said: “The endolysins could be incorporated into the DNA of probiotic strains so that these bacteria produce endolysins once they have colonised the gut.

“The endolysins will only target the pathogenic bacterial strain, which is a great advantage over the use of antibiotics. Whether GMO yoghurt will be eaten by the public is another question.”