Fighting bacteria with viruses: The role of phages in medicine

Deep within the microscopic world, an ancient battle unfolds. Bacteria multiply rapidly, claiming space and resources, while their natural viral predators—bacteriophages—lie in wait, ready to strike. 

These tiny viruses can hunt precisely, latching onto bacteria to inject their genetic material and turn them into viral factories before causing them to burst. Though invisible to the naked eye, this microscopic competition has shaped life for billions of years. Now, scientists are exploring phages to combat antibiotic resistance and restore microbiome balance, particularly in the fight against superbugs—bacteria that are resistant to multiple antibiotics, making infections more challenging to treat. 

How serious are these challenges? 

According to the CDC, over 2.8 million antimicrobial-resistant infections occur in the U.S. each year, causing more than 35,000 deaths. Meanwhile, imbalances in the microbiome, or dysbiosis, are linked to chronic health conditions like inflammatory bowel disease, metabolic disorders and mental health disorders. These growing threats demand innovative solutions to manage bacterial overgrowth. 

Bacteriophages offer a targeted solution that antibiotics can’t. 

Bacteriophages, often called phages, specifically infect bacteria by recognizing unique molecular structures on their surfaces. Phages act like microscopic precision tools, akin to guided missiles that home in on their targets. Unlike broad-spectrum antibiotics or antimicrobials, which indiscriminately destroy entire bacterial populations, phages strike with pinpoint accuracy. 

"Phage therapy highlights how nature can inspire innovative solutions to medical challenges. By understanding the strengths and limitations of phages, researchers hope to develop better ways to manage infections and restore balance to the microbiome."

-- Douglas Johnson

Phages recognize specific receptors on bacterial cell membranes (i.e., lipopolysaccharides, teichoic acids or outer membrane proteins), ensuring they only infect certain strains. If a bacterium lacks the correct receptor, the phage cannot attach, making this a precise and adaptable tool for bacterial control. 

Once attached, the phage injects its genetic material into the bacterial cells, hijacking its internal machinery to produce new phages. As replication continues, the bacterial cell eventually bursts, releasing the newly formed phages to infect more bacteria. 

This precision makes them a promising tool for treating infections while preserving the body’s microbiome. 

The idea of using bacteriophages to target bacteria isn’t new. It dates to the early 20^th century when British bacteriologist Frederick Twort and French-Canadian microbiologist Félix d’Hérelle discovered phages independently. In 1919, d’Hérelle successfully treated a 12-year-old boy with severe dysentery using a phage preparation, leading to a full recovery within days. 

In the 1920s and 1930s, phages were often used as treatments, but the rise of antibiotics in the 1940s—a more convenient and widely available alternative—shifted focus away from them. However, phage therapy didn’t entirely vanish. Research continued in Eastern Europe, where countries like Poland maintained active phage research and application programs. 

In the last decade, phage therapy has resurged globally, including in the U.S. In 2016, mirroring the success of d’Hérelle almost a century earlier, epidemiologist Steffanie Strathdee collaborated with an international team to use phage therapy alongside antibiotics to save her husband, Thomas Patterson, from a life-threatening multidrug-resistant Acinetobacter baumannii infection. Their journey is detailed in their book, The Perfect Predator, and highlights the opportunity to use these viruses to our advantage. 

Now institutions such as Yale University and the University of California, San Diego have established dedicated centers for phage research and therapy. The National Institutes of Health (NIH) has also recognized its potential. In 2021, the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) awarded grants to support research addressing key knowledge gaps in developing phages as preventive and therapeutic tools. 

Today, antibiotic resistance is on the rise, causing once-treatable infections to become more challenging—and sometimes impossible—to cure. More concerning, the development of new antibiotic classes has slowed dramatically. Since the 1980s, most newly approved antibiotics have been modifications of existing drug classes rather than genuinely novel treatments, making it easier for bacteria to develop resistance. The high cost and lengthy approval process for new antibiotics have further discouraged pharmaceutical investment. As a result, phage therapy is gaining global interest as scientists explore its potential in modern medicine. 

"Phages act like microscopic precision tools, akin to guided missiles that home in on their targets."

-- Douglas Johnson

Beyond combating bacterial infections, phage therapy is also being explored to address microbiome dysbiosis. For example, by selectively targeting harmful bacteria, phages can help restore balance to the gut microbiota, potentially alleviating conditions associated with dysbiosis, such as gastrointestinal and liver diseases. 

With all this promise, why isn’t it widely available yet? 

Despite its potential, several obstacles prevent phage therapy from becoming a mainstream treatment. One of the biggest challenges is the time-intensive process of identifying which phage— or combination of phages (phage cocktail)—will be effective for a specific infection. Because phages are highly specific, a single type may only work against a narrow range of bacterial strains. This means a care team must first isolate and characterize the infectious bacteria before matching with the appropriate phage, which can take days to weeks. In acute infections, this delay could limit its clinical usefulness. To address this, researchers are developing phage libraries, pre-selected cocktails and rapid screening methods to streamline this matching process. 

Beyond identification, other hurdles must be addressed before phage therapy is widely adopted. One concern is how the immune system responds to phages, as the body might recognize them as invaders and eliminate them before they can be effective. Additionally, when phages lyse (break open) bacterial cells, they can trigger endotoxin release syndrome, a condition where bacterial toxins flood the body, potentially causing widespread inflammation. Lastly, large-scale production of phages remains a complex and lengthy process, requiring strict quality control to ensure purity, stability and consistency between batches. Overcoming these challenges is essential for integrating phage therapy into modern medicine as a reliable alternative. 

To begin to address some of these barriers, scientists are looking to genetic engineering, which allows researchers to modify phages to target a broader range of bacteria or enhance their effectiveness. Though still in development, these approaches could help integrate phage therapy into mainstream medicine and provide new tools to fight against bacterial overgrowth. 

Ultimately, phage therapy highlights how nature can inspire innovative solutions to medical challenges. By understanding the strengths and limitations of phages, researchers hope to develop better ways to manage infections and restore balance to the microbiome. As issues like antibiotic resistance and dysbiosis continue to grow, phage therapy offers a hopeful avenue for future exploration—one that may redefine how we target bacteria.