One Phage Cocktail, Please

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Increasing antibiotic resistance is hitting the headlines at the moment, and a genuine concern is growing, amongst the public and scientists alike, over the concept of a future without antibiotics. Research attention is beginning to focus on possible solutions, but some may be old, rather than new.

In the second half of the 20th Century, patients suffering from bacterial infections behind the Iron Curtain were denied access to the antibiotics that were saving lives in the west. Instead, many of these people were treated with phage therapy, which makes use of viral bacteriophages which kill bacteria. Phage therapy never really caught on, however, at least in part because bacteriophages are highly specific (meaning you need to know exactly what has infected your patient to be able to treat effectively) and because people are inherently uneasy about treating an ailment using a virus. Interest has renewed recently however, in light of major concerns over antibiotic resistance, and the European Commission has just invested €3.8 million into a large-scale clinical trial of phage therapy.

Inexhaustible Variety

In the fight against bacterial infectious disease, our biggest problem is that our foe is a living organism, capable of evolving. This means we are locked into a never-ending arms race with our bacterial enemies – for every solution we find, they will eventually find a defence. We’re seeing this problem now, as we begin to run out of effective antibiotics. Bacteriophages are part of an evolutionary arms race that viruses have been fighting with bacterial for millions of years, and one way that viruses have succeeded in battling bacteria is through variety. There is an almost inexhaustible supple of different bacteriophages in nature. In fact, nobody has ever found two the same. So phage therapy could be extremely effective, long-term, because as bacteria develop resistance to one phage, we simply use another. Using a cocktail of phages together could be our best best in treating highly resistant bacteria. Researchers have suggested that phage therapy might be used in a similar way to seasonal influenza vaccines – updated every year as new strains emerge. However, more research is needed to devise the best strategic application of phage therapy to bacterial infections.

A Targeted Missile

The specificity of viral bacteriophages might turn out to be an asset rather than a curse. Broad spectrum antiobiotics have been a favourite amongst doctors for decades because they treat a huge variety of different bacterial infections. However, because they are non-specific, these antibiotics can also harm our natural microbial populations, many of which are beneficial. Bacteriophages attack only the target of interest, and so when used appropriately, could have the same medicinal benefits of antibiotics with fewer side effects and a reduced risk of complications.

Phages on Trial

Plans were recently unveiled for a major, multi-centre clinical trial of phage therapy for human infections, funded by the European Commission – Phagoburn. Phagoburn will begin trials in September 2014, and researchers across Europe plan to recruit over 200 burn victims with bacterial infections from common bacteria such as Escherichia coli or Pseudomonas aeruginosa. Patients will be treated with phage cocktails made in France using phages isolated from over 1000 viruses sourced from nature. If the treatment is unsuccessful, patients will be treated with traditional antibiotics instead.

Researchers at the Massachusetts Institute of Technology have also been investigating how engineered phages might help in the fight against antibiotic-resistance. By genetically engineering a phage to incorporate a DNA-editing system called CRISPR they hope to target only antibiotic-resistant bacteria. In early trials, their phage killed 99% of E.coli cells containing specific antibiotic-resistance genes, but left antibiotic susceptible cells intact.

Money Matters

Although it shouldn’t be, money is a major issue for dealing with antibiotic resistance. One of the reasons we are running out of effective antibiotics is because it has become unprofitable for pharmaceutical companies to invest in developing new ones. Phages may also not be a favourable option for those who wish to profit from healthcare – since phage therapy was developed nearly a century ago, treatments are unlikely to be suitable for patent. Further, a US Supreme Court ruling in 2013 against the patenting of naturally occurring genes, would make phage discovery a poor prospect for making money. Engineering phages would be a different matter, of course. Of course, while cynics might criticise a system that requires human health interventions to be profitable, the reality of the matter is that anybody who is going to invest millions of dollars into developing new therapies does need a way to recoup their costs. Importantly, though, we cannot allow potentially life saving treatments to go unresearched simply because they are not profitable enough. Government-funded research may lead the way in the development of phage therapy and other solutions to the growing antibiotic resistance crisis.

Want to Know More?

Reardon (2014) The Rise of Antibiotic Resistance Rekingles Interest in a Century-Old Virus Treatment Nature News

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