Clostridium difficile is a bacteria that can cause severe illness in humans. Uncontrolled proliferation of C. difficile is observed primarily in patients with significant disruptions to the intestinal microbiota due to long-term antibiotic therapy. Toxins produced by C. difficile cause diarrhea and severe inflammation and damage to the colonic mucosa, a condition known as pseudomembranous colitis. C. difficile infection has become increasingly common in recent years.

Treatment for C. difficile infection involves a course of antibiotics. Treating an illness caused by antibiotic use with antibiotics may not be the best solution, as the cause of C. difficile proliferation is significant disruption of the gut microbiota, and such treatment can only worsen the condition. Therefore, relapses of C. difficile infection are very common after treatment. The spread of antibiotic resistance among C. difficile strains adds to the problem.

In Norwich, Norfolk, UK, scientists are exploring the possibility of treating C. difficile infection with bacteriophages specific to the bacterium. They screened 27 strains of C. difficile and discovered a previously undescribed bacteriophage, dubbed ΦCD27 (phiCD27). Its genome exhibited sufficient distinctiveness for members of the International Committee on Taxonomy of Viruses (ICTV) to confirm that it represents a new group (genus) of phages. The new genus of bacteriophages was named Colneyvirus, after the street in Norwich on which the Institute of Food Research, where the new virus was discovered, is located. Since then, four more species of Colneyvirus have been discovered, and the ICTV has officially recognized the new genus of bacteriophages, Colneyvirus.

Phages replicate, using the bacteria's synthetic systems and resources to create new viral particles. Once the particles are ready, specialized phage enzymes—endolysins—break down the bacterial wall, and the phages are released.

Researchers identified the endolysin gene in the phiCD27 colivirus genome and inserted it into the E. coli genome to produce a pure protein. The enzyme, synthesized in this "microbiological factory," was found to be active against 30 different strains of C. difficile , including the currently common hypervirulent ones.

Importantly, these endolysins kill only C. difficile . This means, unlike antibiotics, they do not affect other bacterial species that inhabit the human colon and are part of its normal microbiota.

However, to destroy C. difficile, endolysins (common proteins easily destroyed in the gastrointestinal tract) must be delivered to the large intestine. To this end, scientists inserted the endolysin gene into lactobacilli, which easily reach the lower intestine, replicate, and begin synthesizing the necessary protein. Experiments are ongoing, but the scientists hope that their proposed approaches will help combat C. difficile infection* .

* Mayer MJ, Narbad A, Gasson MJ. Molecular characterization of a Clostridium difficile bacteriophage and its cloned biologically active endolysin. J Bacteriol. 2008; 190 (20): 6734-40. doi:10.1128/JB.00686-08.