Local grant boosts UT Health San Antonio scientist’s mission to advance phage therapy

Since the discovery of antibiotics, physicians have grappled with the inevitability of bacterial resistance to antibiotics. This challenge has become increasingly urgent, with antibiotic resistance projected to cause 39 million deaths between 2025 and 2050, according to the World Health Organization. By 2050, the organization also predicts these infections will surpass cancer as the leading cause of death worldwide. One potential solution lies in harnessing naturally occurring bacteria-eaters known as bacteriophages, or phages.

Pioneering phage research in San Antonio

Philip Serwer, PhD, a professor of biochemistry and structural biology in the Joe R. and Teresa Lozano Long School of Medicine at The University of Texas Health Science Center at San Antonio (UT Health San Antonio), has devoted his career to studying phages and their therapeutic applications. In the fall of 2024, the San Antonio Medical Foundation awarded a grant of approximately $200,000 to a collaborative team that includes Serwer and scientists at The University of Texas at San Antonio, Texas Biomedical Institute and Brooke Army Medical Center. This team aims to advance phage research and develop treatments for multi-drug-resistant bacterial infections.

"This work is highly exploratory but already producing results beyond the scope of our initial proposal," Serwer said.

Expanding the scope of phage research

Serwer's previous research, supported in part by a 2023 San Antonio Medical Foundation grant, explored the hypothesis that phages with the highest persistence had a greater negative electrical charge on their surfaces, making them better candidates for phage therapy. Under this most recent grant, researchers will have two main objectives:

• Further develop a newly discovered strategy for increasing phage persistence. A critical hurdle in phage therapy is the variation in persistence-how long phages remain in the bloodstream. Without sufficient persistence, phages cannot effectively combat infections.
• Use basic science advances made by students in the Department of Microbiology, Immunology and Molecular Genetics at UT Health San Antonio to obtain improved therapeutic phages for use against pathogens. Toward this aim, Serwer's team is collaborating with Larry Schlesinger at Texas Biomedical Research Institute, a globally recognized expert in pathogens and infectious diseases, particularly tuberculosis.

History and challenges of phage therapy

Phages, classified as viruses, are harmless to humans and are found in soil, water, humans and just about anywhere with bacteria. Though phages were discovered over a century ago, the advent of antibiotics sidelined their widespread therapeutic use due to its complexity and, primarily, the inconsistency of its success. Unlike antibiotics, phages are highly specific, targeting only certain bacteria without harming beneficial microbes. However, this specificity also poses challenges. Treating an infection may require multiple phages, and doctors must precisely identify the bacterial strain to select the right phage.

Currently, phage therapy is approved in the United States only for special cases where all antibiotic treatments have failed. More research showing the safety and efficacy of phage therapy could lead to broader use and acceptance in the U.S.

Tackling persistence and production challenges

In previous studies, Serwer's team discovered ways to measure and enhance phage persistence. They developed more efficient procedures for isolating phages and projecting the likelihood of high persistence, including use of native (intact phage) agarose gel electrophoresis, pioneered by Serwer decades ago for use in phage research.

Groundbreaking work revealed that low-persistence phages could develop higher persistence. Moreover, these high-persistence phages could transfer their high persistence to other, lower-persistence phages, paving the way for large-scale production and isolation of effective phages.

Other key advances include isolation of a unique phage that bypasses bacterial resistance and the development of improved methods for therapeutic delivery of phages, sometimes in a dry state.

"Integrating the basic science with phage-based biomedicine would produce a major advance in phage therapy of bacterial disease and, also, phage-based therapies of other diseases," Serwer said.

Building a phage therapy hub in San Antonio

To succeed with phage-based therapies, Serwer outlined three key requirements: a company managing commercial products, clinician interest and additional scientific input. Progress has already been made on all three fronts.

"Our work has already produced discoveries that have the potential to transform the field," Serwer said.

Phage Refinery, a company co-founded by Serwer, James P. Chambers of UTSA, and entrepreneur William Tolhurst, is at the forefront of commercializing phage research. The company has assembled a team of scientific advisors and is creating an open database to facilitate information-sharing among phage researchers worldwide. Developing a comprehensive database of phages and the bacteria they target is a crucial step toward making phage therapy more accessible and effective.

Through the San Antonio Medical Foundation's connections, the team has partnered with Patrick Ng, MD, associate professor and researcher in the Department of Emergency Medicine at UT Health San Antonio, to bridge the gap between research and clinical application.

"The goal is to have all needed components readily accessible, possibly all in San Antonio," Serwer said. "Suppose somebody says, 'I have an infection. Can I come to San Antonio to be cured?' Achieving this goal moves us closer to the point that the answer is 'yes' for a wide range of infections."

A vision for the future

Serwer is interested in worldwide interactions to achieve this goal, especially for the isolation, testing and modification of the various phages needed. San Antonio is progressively becoming positioned to be the hub for this venture. The integration of phage isolation, preparation and clinical treatment by a single hub would be a significant development for phage therapy.

"The goal is to create the most extensive integration of science and medical practice here in San Antonio," he said.

As the threat of antibiotic resistance grows, this integration offers hope for effective, long-lasting treatments using a relatively direct, safe, rapidly adapted strategy based on nature's own bacteria-eaters.

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