Viruses have a menacing reputation for causing disease but some that target bacteria could actually benefit human health.
These are called bacteriophages, and a group of them named after the Norfolk village of Colney could help combat C. difficile infections.
Clostridioides difficile, also known as C. diff, is a species of bacteria that infects the human gut. It can become a major problem when our normal gut microbes are impaired, most commonly during a course of antibiotics. This leads to an overgrowth of C. difficile, with toxins it produces causing diarrhoea and severe inflammation.
Treatment involves further courses of antibiotics, but relapse and recurrent infections are common. The strains are becoming more resistant to antibiotics and more capable of causing severe disease so there is a clear need for other treatments.
Clostridioides virus phiCD27 of the genus colneyvirus. The phage is about 300nm long, meaning about 200 would fit across the width of an average human hair. Transmission electron microscopy image by Mary Parker
This drove researchers in Norwich to look for the bacteria’s natural enemy, bacteriophages. They screened 27 different C. diff strains for any bacteriophages, finding one, which they called ΦCD27 (phiCD27). Genome sequencing confirmed this phage had not been discovered before. In fact, the members of the International Committee on Taxonomy of Viruses (ICTV) decided it was genetically distinct enough to form a new group, or genus of phages.
The ICTV decided to name the new genus Colneyvirus, after the address on Colney Lane of the Institute of Food Research (IFR) on the Norwich Research Park, where it was first discovered. IFR has since transitioned into the Quadram Institute and moved to a new building, also within the civil parish of Colney. Although the parish of Colney has a population of only about 120 people, it is still “home” to four world-leading research institutes, one of the UK’s largest teaching hospitals, plus a Premier League football team.
Four other species of colneyvirus have since been identified and in June the ICTV announced the official creation of the Colneyvirus genus.
But what C. diff busting weapons does the first colneyvirus have it have in its arsenal?
Phages exist and reproduce by injecting their genetic material into bacteria, and using the host’s own machinery to construct new viruses inside the cell. They then release enzymes called endolysins that destroy the bacterial cell wall, releasing the new viruses.
The researchers found the gene for ΦCD27’s endolysin in the genome sequence and put it into another bacterium, E. coli so that they could produce and purify the endolysin. They found that it was active against 30 different C. diff strains, including hypervirulent strains behind the current epidemic. Importantly, the endolysin didn’t affect other bacterial species that commonly make up the human gut microbiome.
‘’This phage and the endolysin encoded by its genome can provide a targeted approach to combat C. diff infections, in contrast to the use of broad spectrum antibiotics that cause collateral damage by inhibiting other members of the gut bacterial population’’ said Professor Arjan Narbad, Group Leader at the Quadram Institute.
However, to be effective the endolysins need to be delivered into the gut, so the team also put the gene into a strain of lactic acid bacteria that has previously been used to deliver proteins and vaccines to the gut.
The research team believes this provides a platform for future new treatments to combat C. diff. Much more needs to be done to refine the system, but in the battle against this bacterial pandemic, the colneyvirus could be a vital ally.
Colney Lane in 2016, snaking SE to NW across the Norwich Research Park. The old Institute of Food Research buildings can be seen bottom left. St Andrew’s, the parish church of Colney, is bottom right. The building site in the top centre is where the Quadram Institute now stands. Image: Anglia Innovation Partnership LLP
Dr Evelien Adriaenssens, Chair of the Bacterial Viruses Subcommittee, proposed the name colneyvirus with other members of the ICTV. She was not involved in the initial discovery of the colneyvirus phages, but later moved her research to Colney itself, setting up her research group in the Quadram Institute.
“As bacteriophage taxonomists, responsible for classifying and naming new taxa, we always look to honour people, places or institutes involved in the first description of a new group of phages” said Dr Adriaenssens. “In this case, I had the opportunity to help create and name a new genus of phages based on a discovery by my own colleagues, made long before I joined the Quadram Institute. It feels fitting to name the genus after Colney, where so much excellent science is performed.”
The research was funded by the Biotechnology and Biological Sciences Research Council, part of UKRI.
Molecular Characterization of a Clostridium difficile Bacteriophage and Its Cloned Biologically Active Endolysin, Melinda J. Mayer, Arjan Narbad, and Michael J. Gasson Journal of Bacteriology Volume 190, Issue 20, 15 October 2008, Pages 6734-6740 DOI: 10.1128/JB.00686-08