How Bacteriophages Can Save Us From Antibiotic Resistance

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Phage Therapy Has Been Around for A Century, But It Was Pushed Aside for the Very Treatment That’s Losing Its Efficacy.

Photo by Michael Schiffer on Unsplash

What do Streptococcus pyogenes, Neisseria gonorrhoeae, and Acinetobacter baumannii have in common? These are three of 10 bacteria that doctors are worried about, because they are becoming more resistant to antibiotics. S. pyogenes is a deadly virus that can causes sore throat and scarlet fever. It’s got a 25-percent mortality rate. N. gonorrhoeae causes gonorrhea, which has become one of the STDs on the rise, and A. baumannii was prevalent in injured soldiers during the Iraq war, causing pneumonia and meningitis.

Alongside climate change, antibiotic-resistant infections are arguably the biggest threat to human life, because under the right circumstances, a completely healthy individual can die from something as innocent as an infected scratch or a sore throat. Globally, 700,000 die every year due to antibiotic resistance. By 2050, that number could rise to 10 million.

Dire Warnings

Sir Alexander Fleming’s warning about antibiotic resistance

The medical community has been warned about this for decades, especially by Sir Alexander Fleming, the inventor of penicillin. Some of the factors that led to this include patients not finishing the full antibiotic course as prescribed and doctors over-prescribing antibiotics. But, scientists are just learning about how these bacteria become resistant.

Remember the series, Star Trek: The Next Generation? Think of the bacteria like the Borg. Their tentacles, called pili, are like tractor beams, reeling in and assimilating DNA. In the assimilation process, the bacteria absorbs all the information and learns how to counteract the antibiotics’ attack. It successfully evolves to the point that every subsequent antibiotic course is weakened, until they becomes futile. Meanwhile the unchecked bacteria is multiplying and wreaking havoc on your body. With this new knowledge, researchers can figure out how to stop this assimilation process.

It turns out that these bacteria already have a natural predator that does this.

Bacteriophages

The history of bacteriophages goes back to a paper written by Frederick Twort in 1915. He was trying to grow the vaccinia virus, the answer to smallpox, and observed some glassy-looking micrococci that killed off the bacteria on the agar. In 1917, French-Canadian Félix d’Herelle independently found these viruses that killed bacteria and coined the term ‘bacteriophages’, where phage is Greek for ‘a thing that devours.’ During the First World War, French soldiers suffered from dysentery, and d’Herelle found that his new discovery was a natural predator to infectious bacteria.

In the 1930’s d’Herelle met with Georgian microbiologist George Eliava, who had established an institute in 1923 that was dedicated to bacteriophage research and therapy. During this time, Georgia was officially known as the Georgian Soviet Socialist Republic, a part of the Soviet Union under Georgian-born dictator, Jospeph Stalin.

Before the two scientists had a chance to collaborate, Eliava was executed by Stalin. The institute continued its mission, however, and, during the Second World War, they were instrumental in helping the Russian military deal with many of the wound and postoperative infections of the time.

Phage therapy became a staple in Soviet medicine well after the World War II, but in western countries, antibiotics were mainstays, because they were both efficient and much cheaper to produce. As a result they were belittled and not taken seriously as viable infectious disease treatments by western doctors.

With the deepening political chasm between the countries, the thought of bacteriophages faded in the west, but in the then-Soviet Union, knowledge and data increased. Phages were so popular that they were (and are) sold as over-the-counter cocktails for common stomach ailments. Now, doctors are looking to Georgia to help them fight against a rising tide.

Why Phage Therapy Works

Christoph Leberecht [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)]

A bacteriophage looks like something out of science fiction. Its head looks like a polygon, then there’s the screw-shaped body and tentacles coming from bottom, like feet.

So how do they do it?

Here’s another movie reference: Remember the very first Alien movie, where the “baby” that had been gestating in that guy’s stomach just burst out? That’s basically what phages do to bacteria. They use the bacteria as a factory to make more phages, so that when the infectious organism is destroyed, there are plenty more to take care of the others for as long as it takes to get the job done.

What makes them even more special is that they are very specific predators, meaning they will only hunt for the bacteria they were evolved to destroy. For example, if the phage is designed to eliminate E. coli, it won’t go after MRSA, nor will they destroy any of the beneficial bacteria in your body. It’s job is to hunt specific prey without inflicting collateral damage, unlike antibiotics.

Phages work as cocktails of more than one or with other complementary therapies, because they work better in combination than as lone warriors. Interestingly, doctors have discovered that phage therapy not only eliminates infections, but it makes the resistant bacteria more sensitive to antibiotics. By all accounts, phages are the answer modern medicine has been looking for to save tens of millions from dying.

Why isn’t this decades-old solution gaining more traction faster?

The Realities

Despite the fact that this is one of the best options to deal with antibiotic resistance, there are a few reasons why it will take far more than just whipping up a few cocktails.

Mistrust

Unfortunately, the iron curtain hasn’t been fully raised. Though Georgia is now an independent country and has worked hard to reestablish its own identity, the history of the USSR looms large. Many do not trust the science that sustained the citizens of the former Soviet Union, much less the idea that any virus that comes the country, even one that is specifically targeted to kill infectious bacteria, would be safe. While phages aren’t considered alive, they are considered live biological agents, which raises multiple concerns.

The Nature of Phages

As mentioned, phages are very selective, which means you need to know the bacteria you want to target, and then see which phages work against it. As these organisms are everywhere, they can be taken in from a variety of unsavory sources, including animal feces, researched and tested for efficacy. Their range can be extremely narrow, and there are times when they aren’t as effective, and may even result in resistant bacteria. It’s ironic, but possible, according to experts.

Money

Remember, the mass production of drugs such as penicillin, has driven down the price of wellness significantly. The average cost of phage therapy, a practice in which the Eliava Institute is the leading authority, is currently in the thousands, and if you have to do any in-patient therapy from another country, it’s going to be more.

But the main obstacle is…

Regulation

Red tape is always an obstacle, and with this case, it’s no different. You could argue that clinical trials have been around for thousands of years, and while that wouldn’t be wrong, phage therapy began long before formalized clinical trials. Because they don’t have that official history, organizations like the FDA will not readily approve that kind of therapy.

Another regulatory sticking point is that there would need to be a clinical trial for every instance of phage usage. If you want to test the phage for MRSA, that’s one trial. If you want to test the same phage for E.coli, that’s another…you get the idea that this would be long and costly. The FDA just approved their first bacteriophage clinical trial in February 2019, and any form of that kind of therapy regardless of how desperately it’s needed would need to be approved by the FDA.

While you’re at it, consider that the FDA are about a century behind on testing and do your own projections about how long it will take for them to catch up.

Phages are one of the best ways medicine has to deal with growing antibiotic resistance, but the question is, how long will it take before the need to implement reaches critical mass?

Let’s hope that 2050 isn’t closer than we think.


If you want to find out more about phages, check out this BBC podcast that documents a harrowing case of a deadly bacterial infection.

There’s also a great article in Elemental about how a new strain of resistant E. coli caused the death during a fecal matter transplant procedure.

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