Bacterial virus found in Jerusalem sewage proposed to fight root-canal infections

Hebrew University scientists have proposed a way to “trick” harmful bacteria that infect humans by infecting them with viral bacteriophages that gobble up bacteria.

By JUDY SIEGEL-ITZKOVICH
Petri dish [Illustrative] (photo credit: REUTERS)
Petri dish [Illustrative]
(photo credit: REUTERS)
Hebrew University-Hadassah Faculty of Dental Medicine researchers have suggested a new way to kill harmful bacteria that take a heavy toll around the world by cultivating a tiny virus from Jerusalem’s sewage that they believe could prevent root canal infections.
Every year, drug-resistant infections kill more than 50,000 people across Europe and the US, and hundreds of thousands more around the world. According to the Review on Antimicrobial Resistance commissioned in the UK, failing to address the growing problem of drug-resistant infections could cause 10 million deaths a year and cost up to $100 trillion by 2050.
The Hebrew U. scientists have proposed a way to “trick” the tables on harmful bacteria that infect humans by infecting them with viral bacteriophages that gobble them up.
The research will appear in the April 2015 edition of the Journal of Applied and Environmental Microbiology as “Targeting Enterococcus faecalis biofilm using phage therapy;” it already appears on its online edition.
The research team was led by Dr. Ronen Hazan from the university’s Institute of Dental Sciences and Dr. Nurit Beyth from the dental school, together with their co-workers and students Dr. Shunit Glaser, Leron Khalifa, Daniel Gelman, and Yair Brosh.
Just a few decades ago, antibiotics were considered wonder drugs. Ironically, because they worked so well, they were used too often, leading to the rise of drug-resistant bacteria. These untreatable pathogens evolved mutations enabling them to resist the antibiotics that doctors prescribe to fight them.
One such pathogen is Enterococcus faecalis, a bacterium inhabiting the gastrointestinal tracts of humans. This life-threatening pathogen causes diseases ranging from endocarditis (a potentially fatal heart infection) to bacteremia (harmful bacteria in the bloodstream), as well urinary tract infection, meningitis, and post-treatment root canal infections.
E. faecalis is a highly durable strain and is especially difficult to target when assembled in a sticky bacterial cluster called biofilm. E. faecalis is often recovered from persistent infections associated with root canal treatments, and infection may persist in 20 to 33 percent of root canal work.
The frustrating rate of infections reflects the limitations of current treatment options.
Thus the researchers said it is essential to develop additional ways to target highly virulent bacteria such as E. faecalis, especially when in biofilm form.
An alternative “phage approach” instead of giving antibiotics is known as bacteriophage therapy. These viruses play a key role in maintaining the natural balance in their predator-prey relationship with bacteria and co-evolved with their bacterial hosts to be highly effective specific “professional bacterial killers.”
The researchers isolated an anti-E. faecalis phage from sewage effluents retrieved from a Jerusalem sewage treatment facility. The phage, named EFDG1, is able to infect the V583 strain of E.
faecalis, which is resistant to vancomycin – the most effective anti-E. faecalis antibiotic.
The team evaluated EFDG1’s efficacy against E. faecalis cells both in a liquid culture and in biofilm form. Since there are currently no effective ways to eradicate E. faecalis biofilms, the researchers’ goal was to target E. faecalis in its most robust form, as a biofilm.
In both cases, EFDG1 almost entirely eradicated the bacterial cultures. EFDG1 was found to be highly efficient against various E. faecalis and E. faecium isolates, regardless of their antibiotic resistance profile.
The researchers also showed that EFDG1 was highly effective in root canal infection, both in vitro and ex vivo in tissue samples. These findings suggest that phage therapy using EFDG1 might be an effective way to prevent E. faecalis infection following root canal procedures.
To see whether the EFDG1 is safe to use in fighting E. faecalis infections in humans, the researchers examined EFDG1 phages for the presence of hazardous genes. By visualizing the phage using electron microscopy, followed by whole genome sequencing, the researchers found that it belongs to the Spounavirinae subfamily of the Myoviridae phages, which include other promising candidates for therapy against gram-positive pathogens. They proved that the EFDG1 genome does not contain apparent harmful genes.
Hazan explained that “the idea of using phages as anti-bacterial drugs is not new. Phage therapy was first proposed at the start of the 20th century, but then abandoned for various reasons, including the striking success of chemical antibiotics.”
Now, he concluded, “we stand on the verge of a new era with the limitations of synthetic antibiotics and the emergence of antibiotic-resistant strains of bacteria. Thus it is the right time to look again into what Mother Nature offers in the battle against bacteria. As this research shows, bacteriophages may prove an effective tool in the development of much-needed new antimicrobial drugs.”