Bacteriophages are the most abundant biological entities on the planet, a type of virus that specifically infects and replicates within bacteria. The term “bacteriophage” literally means “bacteria eater.” These viruses are found wherever bacteria exist, from soil to oceans and within other organisms, including humans, with thousands of types adapted to infect only specific bacteria. Their composition consists of genetic material, either DNA or RNA, enclosed within a protein shell.
Structure and Lifecycle of a Phage
A bacteriophage’s structure is often compared to a lunar lander. It consists of a polyhedral head, which contains the phage’s genetic material, attached to a tail. The tail has a hollow inner tube surrounded by a contractile sheath and a base plate with long tail fibers that recognize and attach to a specific bacterium.
Once a phage has identified and attached to a host bacterium, it initiates its reproductive cycle. The tail fibers bind to specific receptors on the bacterial cell surface. Following attachment, the phage’s tail sheath contracts, functioning like a hypodermic syringe to inject its genetic material through the bacterial cell wall, leaving the empty protein structure outside.
The subsequent events follow one of two main pathways: the lytic or lysogenic cycle. The lytic cycle is a direct and aggressive process where the phage’s genetic instructions immediately take over the host cell’s machinery. The bacterial cell is forced to stop its own functions and instead begins to translate the viral genes, producing all the necessary components for new phages.
As these components are synthesized, they self-assemble into hundreds of new, complete phage particles inside the host cell. In the final stage of the lytic cycle, the phage directs the production of enzymes that break down the bacterial cell wall from within. This causes the bacterium to rupture, or lyse, releasing a new generation of phages.
The lysogenic cycle offers a more temperate alternative. After the phage injects its DNA, it does not immediately commandeer the cell for replication. Instead, the phage DNA integrates itself into the host bacterium’s own chromosome, becoming a dormant entity known as a prophage. The infected bacterium continues to live and reproduce normally, passing the prophage’s DNA to its daughter cells.
Phage Therapy for Bacterial Infections
Phage therapy is the therapeutic use of lytic bacteriophages to treat bacterial infections. This approach leverages the natural predator-prey relationship between phages and bacteria. A carefully selected phage, or a combination of phages, is introduced to an infection site, where they specifically target and destroy the pathogenic bacteria.
This method stands in contrast to traditional antibiotics. While many antibiotics are broad-spectrum, killing a wide range of bacteria including beneficial ones, phages are highly specific. This precision means that phage therapy can eliminate harmful bacteria while leaving the body’s natural microbiome, such as gut bacteria, largely undisturbed.
The growing crisis of antibiotic resistance has been a major driver for the renewed interest in phage therapy. Phages offer a distinct mechanism of action, so they can be effective against multi-drug-resistant bacteria. Furthermore, phages can be particularly effective against biofilms—dense, protected communities of bacteria that are notoriously difficult for antibiotics to penetrate.
To address the potential for bacteria to develop resistance to a single type of phage, clinicians often use “phage cocktails.” These are mixtures of several different phages that target the same pathogenic bacterium but use different receptors to attach. This multi-pronged attack makes it much more difficult for the bacteria to evolve resistance simultaneously to all the phages in the cocktail.
Discovery and Modern Resurgence
Bacteriophages were first identified in the early 20th century through the independent work of English bacteriologist Frederick Twort and French-Canadian microbiologist Félix d’Hérelle. It was d’Hérelle who coined the term “bacteriophage” and first proposed their use as a treatment for bacterial illnesses. Following these discoveries, phage therapy was explored and utilized, particularly in Eastern Europe and the former Soviet Union.
The trajectory of phage therapy in the Western world took a different course. With the discovery and mass production of penicillin in the 1940s, antibiotics became the dominant focus of medicine. These chemical drugs were relatively easy to manufacture and effective against a wide range of bacteria, which led to a decline in phage therapy research in these regions.
A significant shift occurred toward the end of the 20th century as antibiotic resistance became a global health crisis. The rise of “superbugs”—bacteria resistant to multiple antibiotics—created an urgent need for alternative treatments. This challenge prompted researchers in the West to revisit phage therapy to combat infections that no longer respond to conventional drugs.
This modern resurgence has been fueled by reports of successful treatments in compassionate use cases, where phages were used to save patients with life-threatening infections. The renewed scientific interest is marked by an increase in published research and clinical trials to evaluate the safety and efficacy of phage therapy. This revival combines historical knowledge with modern biotechnology to develop phages as a targeted therapeutic tool.
Specificity and Safety Profile
A defining characteristic of bacteriophages is their host specificity, resulting from billions of years of co-evolution with bacteria. This precision is due to the interaction between the phage’s tail fibers and specific receptor molecules on the surface of the bacterial cell. If a cell does not have the correct receptor, the phage cannot attach and is unable to initiate an infection.
This targeted action is the foundation of the strong safety profile for phage therapy. Because phages are programmed to attack only their bacterial hosts, they are harmless to human, animal, and plant cells. This selectivity means that when used therapeutically, phages do not damage patient tissues or the body’s own beneficial bacteria.
The natural presence of phages in the human body further supports their safety, as they are abundant in the microbiome, particularly in the gut. Clinical applications have reported minimal adverse effects, even when phages are administered intravenously. The main safety considerations in modern therapy involve ensuring the purity of the phage preparation and confirming the phages are strictly lytic.
This inherent specificity makes phage therapy a form of personalized medicine. For a treatment to be effective, the specific bacterium causing the infection must be identified. A phage with the corresponding host range must then be selected from a library or isolated from environmental sources, resulting in a highly targeted treatment.