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What is Phage Therapy?

Bacteriophages, or phages, are viruses that specifically target bacteria. Phage therapy uses naturally occurring or engineered phages to selectively target bacterial pathogens and treat infections.

Phages are the  and are found everywhere bacteria are located—from the soil to our guts. In fact, it is estimated that . This widespread availability and remarkable host specificity make phages attractive candidates for targeted therapeutic applications.

Key Characteristics

• Selected to target harmful bacteria, not beneficial microbes or human cells. 
• Can adapt alongside evolving bacterial resistance.
• Are often effective when antibiotics fail.
• Can be highly specific to particular pathogens.

Why Phage? Why Now?

In the age of antimicrobial resistance, existing drug therapies are becoming less effective. Researchers estimate that 39 million people will die from drug-resistant pathogens over the next 25 years. Against this backdrop, a novel approach to treating bacterial infections is especially compelling.

Phage therapy has demonstrated life-saving potential in individual cases, but the field remains fragmented, due to a number of system-level, scientific and operational challenges. As a result, phage therapy is not yet widely available and is only administered under Compassionate Use/Expanded Access. 

Recognizing both the promise of phage therapy and the growing threat of antimicrobial resistance, ºÚÁÏÕýÄÜÁ¿Health has launched the Phage Therapy Coordination Network and is leading efforts to break down barriers and transform phage therapy from a fragmented field into a coordinated ecosystem.

Phage Structure

Phages are often depicted as consisting of an icosahedral "head" (capsid) that is connected by a "neck or collar" (injection tube) and supported by "legs or tail fibers" that attach to bacterial cell surfaces. In reality, phages are extremely diverse in size, morphology and genomic organization, and this represents only 1 morphological type.

All phages contain a nucleic acid genome surrounded by an outer capsid that protects and facilitates delivery of phage DNA/RNA to new host cells.

Phage Invasion: A Biologial "Lock-and-Key" System

Each phage infects bacterial targets in a species-specific manner by recognizing receptors on bacterial cell surfaces. In other words, phages can only bind to and infect bacteria that contain receptors they recognize. This precision creates a biological “lock-and-key” system. Notably, the effectiveness of phage therapy depends on matching the right phage to its bacterial target.

• Bacteria = the lock.
• Phage = the key.

Following attachment, phages must introduce their genetic material into the host cell to complete infection. Often they accomplish this by puncturing the bacterial cell wall and injecting their genetic material directly into the host cytoplasm.  

Replication Strategies 

Once inside, the phage's genome takes over the cellular machinery of its host, and the phage may pursue a lytic or lysogenic replicaiton cycle.

• Lytic phages immediately hijack their host and force it begin producing new phage copies until the cell bursts, dies and spreads new phage into the surrounding environment.
• Lysogenic (or temperate) phages integrate their DNA/RNA into their host's genome, where it continues to be replicated without direct harm to the host, until an environmental stressor triggers activation of the lytic cycle.

Phage therapy relies on lytic phages only, as the goal is, ultimately, to kill the pathogenic bacteria in order to clear an infection. 

Current Bottlenecks

Despite strong scientific potential, phage therapy faces scientific, regulatory and logistical challenges that no single organization can solve alone. These barriers include, but are not limited to:

• Inconsistent regulatory pathways.
• Fragmented clinical and research data.
• Uncertainty in dosing and treatment strategies.
• Lack of harmonized clinical protocols.
• Challenges in phage identification and matching.
• Manufacturing and scale-up barriers.
• Lack of standardized production and quality practices.
• Gaps in infrastructure and equitable access.