Researchers Publish Case Study, Receive Grant, and Develop Method for Phage Therapy Advancement

Three Global Advances Bring Phage Therapy Closer to the Clinic

Three separate developments in the field of phage therapy—a clinical case study in Australia, a new research center in the United States, and a laboratory technique in the United Kingdom—are addressing critical aspects of using bacteriophages to treat antibiotic-resistant infections.

The clinical partnership VICPhage, between The Alfred hospital and Monash University, published findings from its first patient case in the journal Nature Medicine.

The patient was a 22-year-old man with cystic fibrosis who had severe recurrent infections resistant to most antibiotics. The study found that pre-existing antibodies in the patient's body destroyed the administered phages before they could kill the infection.

As a result of this finding, researchers developed a method to test subsequent patients for pre-existing antibodies against specific phages. The publication's stated aim is to counter publication bias by sharing results even when the clinical outcome was not favorable.

VICPhage Co-Lead and Director of Infectious Diseases at The Alfred, Professor Anton Peleg, stated that the findings help understand patient-phage-bacteria interactions and will inform future phage selection. Dr. Fernando Gordillo-Altamirano, the first author, noted that the case provided insights into testing patients for antibodies before treatment. Professor Peleg added that a large randomized controlled trial is needed to determine phage therapy efficacy.

The Gladstone Institutes received an initial $2 million award from the National Institute of Allergy and Infectious Diseases (NIAID), with potential funding up to $10 million over five years, to establish the Center for PhAIge Therapy.

The center is part of a coordinated effort across three institutions to advance the therapeutic use of phages against ESKAPE pathogens. These pathogens—Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species—are listed as priority pathogens by the World Health Organization.

The research plan for Gladstone investigators includes:

• Generating data on phage-bacteria interactions.
• Training artificial intelligence (AI) models to predict effective phages for specific infections.
• Focusing on Klebsiella pneumoniae, which can cause pneumonia, bloodstream infections, and meningitis.
• Engineering phage genomes and characterizing bacterial susceptibility to phages.
• Developing algorithms for phage-bacteria compatibility.
• Using human lung organoids to study the effect of body environment on phage behavior.

Two other centers are participating in the effort:

• Stanford University: Focuses on phage delivery to the lung.
• University of Pittsburgh: Develops assays for designing and dosing phage cocktails.

The three centers will share assays, materials, and data.

Researchers at the University of Leicester's Becky Mayer Centre for Phage Research developed a technique to sequence bacteriophage genomes directly from individual plaques on agar plates. The method combines minimal DNA input with amplification and Oxford Nanopore sequencing, enabling rapid genome analysis without large-scale phage purification.

Dr. Andrew Millard, co-lead of the phage center, stated that the method eliminates the need for large-scale purification and reduces the time to analyze hundreds of genomes from months to less than a week. Professor Martha Clokie, also leading the centre, described this as a step toward making phage therapy practical, noting that antimicrobial resistance causes approximately five million deaths annually.

The technique is intended to facilitate the creation of large, characterized phage libraries, potentially accelerating the development of phage therapies for drug-resistant infections. The researchers stated their aim is to integrate phage therapies into routine healthcare.