Phages: A better tool than another round of antibiotics?
There are more phages on earth than every other organism combined, including bacteria, and yet, most people have never heard of them. If you’re new to phages, welcome! These helpful viruses might be our best (secret) weapon against multi-drug resistant bacteria.
First things first: What’s a phage?
Wondering how EcoPhage works? The phages in EcoPhage target E. coli and prevent them from becoming pathogens.1,2 Or attack and kill them if they go rogue. They’re like good cops standing by to maintain and restore order and contribute to healthy gut diversity.
Bacteriophages, or phages, are viruses that infect bacteria and (typically) destroy them. (The word bacteriophage literally means “bacteria eater.”) Like other viruses, phages are made up of a nucleic acid — aka DNA or RNA — surrounded by protein.
When they encounter specific bacteria, phages attach themselves to the bacteria and infect it. They’re said to be the deadliest killers on the planet. They’re also strain-specific, meaning that there is probably a phage for every bacterium on earth.
Once inside a bacterium, phages take two approaches — lysis or lysogenesis:
1. In the first case, lysis, the phage takes over the bacterium’s cellular machinery and stops it from producing its own cellular components. Instead, the bacterium is forced to reproduce more phages. As their number expands into the trillions, the bacterium swells and explodes, killing the host and releasing more phages in the bloodstream.
Now, imagine trillions of greedy phages rushing to invade more bacteria of that same species. It doesn’t take long for the “vicious warriors” to do their job and clean up all the pathogenic bacteria, especially if you start them early. They’re harmless to good bacteria, and they’re protecting you.
2. In the case of lysogenesis, the phage doesn’t kill the host directly. Rather, it sneaks its own DNA into the genetic material of the bacterium in a process called transduction. This means the phage DNA is copied and passed along as the bacterium itself reproduces. This helps to spread the genetic material of phages, some of which then go on to lyse their new hosts.
Some phages switch between a lytic and lysogenic life cycle, while others can only reproduce through lysis. Why does this matter? Because if we want to use phages as Nature’s preventive medicine, we need to know which ones infect which bacteria and how these reproduce.
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Is it true that phages can conquer E. coli?
One especially interesting phage is called lambda and infects Escherichia coli (E. coli).1 Some subspecies of E. coli are responsible for serious infections.
They’re often the cause of symptoms of food poisoning, like:
- Loss of appetite and/or nausea
- Low-grade fever (in some cases)
- Stomach pains and cramps
- Watery and/or bloody diarrhea
The lambda phage can switch between lytic and lysogenic cycles, making it particularly useful in combating E. coli as it can keep up with the bacterium’s own reproduction and keep killing new bacteria.2
In some ways, we might start considering phages as preventive medicine, helping to keep bacteria like E. coli in check so that they don’t become pathogenic. As with probiotics, we may see a future where we take a phage supplement daily to provide protection in case we encounter unpleasant bacteria like E. coli. (A bottle taken on a trip to Mexico could be used as a prophylactic.)
Phage therapy might also be a great remedy if you discover that a meal you’ve recently eaten at a restaurant has been associated with an outbreak of E. coli or some other pathogenic bacteria. And for the many of us who dine on raw fruits and vegetables, yes, even raw fruits and veggies can be infected with bacteria.
What about superbugs? Phages prevail here, too.
Phages have also been seen to effectively fight and destroy bacteria that are resistant to a variety of common antibiotics.
Phage therapy has been proposed as a “traditional” remedy for modern-day superbugs, especially given that, unlike antibiotics, these phages have no known side effects or health concerns. They solely kill and selectively target bacteria.
Unfortunately, current regulations limit phage therapy, except in cases where there is deemed no alternative.3 Thankfully, research is finally filling in the gaps required by regulators as to how phages work their magic.4,5
Phages aren’t new: They’re older than antibiotics.
While many people are learning about phages for the first time, numerous scientists and physicians have known about these viruses since the early 1900s. Indeed, bacteriophages were first discovered in 1915 by William Twort. Then, in 1917, Felix d’Herelle realized that phages could kill bacteria.
Before antibiotics were discovered, bacteriophages were the go-to treatment for bacterial infections and disease. As with so many things, the promise of shiny, new antibiotics proved too tempting, and phage therapy was thrown by the wayside in most parts of the world. In a handful of countries — namely, Russia, Poland, and Georgia — phage therapy remained (and remains) in use to treat a wide range of diseases.6
Thank goodness, because while the use of phages was largely abandoned by the English-speaking world, the research has continued. Most of this research has, however, focused on phages that primarily infect E. coli. Still, we have phage research to thank for our understanding of genetic material and the three-nucleotide code for an amino acid.7
In recent years, phages have enjoyed something of a renaissance, with researchers greatly expanding the number of phages under investigation as potential therapeutic agents.
This has been helped in part by epifluorescent and electron microscopy — which have revealed the impressive presence of phages in bacteria-rich environments, as well as in the genomes of bacteria themselves.
For years, the way in which phages interact with bacteria and human hosts was poorly understood. Now, with advanced genetic sequencing more widely available, researchers have begun to figure out the lytic and lysogenic mechanisms through which phages kill bacteria.
With this newfound knowledge, we could begin to see more phages used to modulate the microbiome and restore balance (eubiosis) in cases where the beneficial microbes have been overrun by pathogenic bacteria. This would have significant impacts in health conditions connected to microbial imbalance, including immunological issues, digestive upsets, and even mental health concerns linked to the gut-brain axis.
Phages versus antibiotics: May the best medicine win.
Unlike antibiotics — which, let’s face it — are a bit of a blunt sword, phages selectively target specific bacteria and are harmless to plants and animals, including humans.
Antibiotics don’t just kill pathogenic bacteria. They can also kill beneficial microorganisms, which then leaves the door open for pathogens to move back in and quickly take over again. (Hence, some of the side effects of antibiotics include diarrhea and digestive upset, among others.)
Antibiotics have also led to the rise of superbugs that are resistant to multiple drugs. Phages don’t pose that risk as they only target one kind of bacteria and, therefore, don’t create conditions for mutated versions of other bacteria to thrive.
Indeed, this selectivity is one of the key benefits of phages. Each phage will only attack a certain bacterium, meaning we could develop specific phage therapies targeted at, say, strep throat or Salmonella.
When it comes to their benefits, phages:
- Are non-toxic.
- Are unlikely to create multiple-drug-resistant superbugs.
- Can be very cost-effective — a fraction of antibiotics and other drugs.
- Continue to be safe to use alongside other medications.
- Don’t harm the beneficial bacteria you want to remain in your gut.
- May be used to fight against antibiotic-resistant bacteria.
- May often be used as a one-dose therapy because they continue to multiply during treatment and keep destroying their target bacteria.
The unfortunate news? Phage therapy isn’t widely available for all the many pathogenic bacteria we could potentially face. At least not just yet.
Still, keep your fingers crossed and, in the meantime, be sure to work with your doctor to identify and treat any bacterial infections you may encounter. Remember the importance of a healthy microbiome for prevention and for immunity and keep up your current probiotic and prebiotic regimen. And, consider Body Ecology’s EcoPhage for support in cases of E. coli infection.1,2
- 1. W.C. Nierman, T.V. Feldblyum, Genomic Library, Editor(s): Sydney Brenner, Jefferey H. Miller, Encyclopedia of Genetics, Academic Press, 2001, Pages 865-872, ISBN 9780122270802, https://doi.org/10.1006/rwgn.2001.0559.
- 2. Sergueev K, Court D, Reaves L, Austin S. E.coli cell-cycle regulation by bacteriophage lambda. J Mol Biol. 2002 Nov 22;324(2):297-307. doi: 10.1016/s0022-2836(02)01037-9. PMID: 12441108.
- 3. McCallin S, Sacher JC, Zheng J, Chan BK. Current State of Compassionate Phage Therapy. Viruses. 2019 Apr 12;11(4):343. doi: 10.3390/v11040343. PMID: 31013833; PMCID: PMC6521059.
- 4. Yi Duan, Cristina Llorente, Sonja Lang, Katharina Brandl, Huikuan Chu, Lu Jiang, Richard C. White, Thomas H. Clarke, Kevin Nguyen, Manolito Torralba, Yan Shao, Jinyuan Liu, Adriana Hernandez-Morales, Lauren Lessor, Imran R. Rahman, Yukiko Miyamoto, Melissa Ly, Bei Gao, Weizhong Sun, Roman Kiesel, Felix Hutmacher, Suhan Lee, Meritxell Ventura-Cots, Francisco Bosques-Padilla, Elizabeth C. Verna, Juan G. Abraldes, Robert S. Brown, Victor Vargas, Jose Altamirano, Juan Caballería, Debbie L. Shawcross, Samuel B. Ho, Alexandre Louvet, Michael R. Lucey, Philippe Mathurin, Guadalupe Garcia-Tsao, Ramon Bataller, Xin M. Tu, Lars Eckmann, Wilfred A. van der Donk, Ry Young, Trevor D. Lawley, Peter Stärkel, David Pride, Derrick E. Fouts, Bernd Schnabl. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease. Nature, 2019; DOI: 10.1038/s41586-019-1742-x.
- 5. Edison J Cano, Katherine M Caflisch, Paul L Bollyky, Jonas D Van Belleghem, Robin Patel, Joseph Fackler, Michael J Brownstein, Bri’Anna Horne, Biswajit Biswas, Matthew Henry, Francisco Malagon, David G Lewallen, Gina A Suh. Phage Therapy for Limb-threatening Prosthetic Knee Klebsiella pneumoniae Infection: Case Report and In Vitro Characterization of Anti-biofilm Activity. Clinical Infectious Diseases, 2020; DOI: 10.1093/cid/ciaa705.
- 6. Chanishvili, Nina. (2012). A literature review of the practical application of bacteriophage research. A Literature Review of the Practical Application of Bacteriophage Research. 1-292.
- 7. Clokie, Martha R. J., and Andrew M. Kropinski. Bacteriophages: Methods and Protocols. Humana Press, 2010.