Phage Therapy

Overview

Phage therapy uses bacteriophages — viruses that infect and lyse specific bacteria — as precision antimicrobials. Unlike broad-spectrum antibiotics, phages target specific bacterial species or strains, sparing the commensal microbiome. In the WikiBiome framework, phage therapy represents a targeted ecological intervention (Karen's Brain Primitive 5) — suppressing specific pathobionts without collateral dysbiosis.

Advantages Over Antibiotics

• Species-specific: Each phage infects a narrow host range, preserving the broader microbiome.
• Biofilm penetration: Phages encode depolymerases that degrade biofilm extracellular matrix — addressing the biofilm resistance problem that defeats antibiotics.
• Self-amplifying: Phages replicate at the site of infection, increasing in number where the target pathogen is most abundant.
• Co-evolution capacity: Phage-resistant bacterial mutants often lose virulence factors, creating a fitness trade-off.

Clinical Evidence

• Chronic prostatitis: Phage endolysins tested against biofilm-forming bacteria in chronic pelvic pain syndrome stevens 2023 phage endolysin cpps chronic prostatitis.
• E. coli prostatitis case report: Phage therapy cleared dominant E. coli biofilm, unmasking co-infecting Serratia marcescens — demonstrating polymicrobial complexity johri 2023 phage therapy ecoli chronic prostatitis case.
• Safety/efficacy systematic review: Phage therapy is generally safe with favorable outcomes in compassionate-use settings, though RCT evidence remains limited uyttebroek 2022 phage therapy safety efficacy systematic review.
• CRC virome: Altered bacteriophage communities in CRC, with phage-bacteria dynamics influencing tumor progression ho 2024 colorectal cancer virome alterations persistence surgery.
• Phage nanovectors: Engineered phage (M13) as drug delivery vehicles for photodynamic CRC therapy turrini 2024 m13 phage nanovector photodynamic crc.

Phage Cocktails

Phage cocktails combine multiple phages targeting the same species (different receptors) or different species in a polymicrobial infection. The cocktail approach:

• Reduces emergence of phage-resistant mutants.
• Broadens the host range within a target species.
• Can address polymicrobial biofilms when combined with functional shielding-disrupting antifungals.

Metal Connection

Phage therapy intersects with metallomics in two ways:

1. Some phage endolysins are zinc-dependent metalloenzymes — zinc availability affects lytic activity.
2. Phage therapy can replace antibiotics in scenarios where metal-antibiotic co-selection (co selection) drives AMR — phages exert no metal-resistance selection pressure.

Cross-References

• antimicrobial resistance — phage therapy as AMR solution
• biofilm — phage depolymerases penetrate biofilm matrix
• functional shielding — sequential antifungal + phage approach for polymicrobial biofilms
• co selection — phage therapy avoids metal-antibiotic co-selection