Scientists Harness Jumbo Viruses to Combat Drug-Resistant Bacteria
UC San Diego researchers are exploring a novel approach to tackle the rising threat of drug-resistant bacterial infections by utilizing large viruses known as bacteriophages. These microscopic organisms, which primarily target bacteria, are gaining attention as potential allies in the fight against infections that traditional antibiotics can no longer effectively treat.
Historically, bacteriophages, or “phages,” have been recognized for their ability to infect and kill bacteria. However, their potential as therapeutic agents was overshadowed by the advent of antibiotics in the mid-20th century. As antibiotic resistance has surged in recent decades, leading to approximately 1 million deaths annually from 1990 to 2021, researchers are revisiting phage therapy as a viable treatment option.
Evolutionary Arms Race
The relationship between bacteria and viruses is characterized by an ongoing evolutionary battle. Bacteria continuously adapt to combat viral attacks, prompting viruses to evolve new strategies to infect these resilient organisms. This relentless competition has encouraged scientists to seek innovative solutions, particularly as drug-resistant bacteria emerge as a significant public health concern.
Recent discoveries at UC San Diego have shifted the focus towards larger phages, termed “jumbo phages.” These organisms, while tiny—about 1/500th the diameter of a human hair—are larger than the human-infecting coronavirus. Advanced imaging techniques, such as cryo-electron microscopy and cryo-electron tomography, have enabled researchers to investigate the biological functions of these phages in unprecedented detail.
In 2022, a team led by professors Joe Pogliano, Elizabeth Villa, and Kevin Corbett unveiled that jumbo phages possess a unique compartment resembling a eukaryotic cell nucleus. This compartment, formed by a protective protein, safeguards the phage’s genetic material, essential for replicating within bacterial hosts. This remarkable finding, according to Villa, is “unlike anything seen elsewhere in nature,” and has led to the classification of this type of phage as chimalliviruses, named after the ancient Aztec shields.
Innovative Treatment Strategies
In collaboration with researchers at the J. Craig Venter Institute and Yale University, UC San Diego aims to leverage these discoveries to engineer phages that can effectively target various antibiotic-resistant bacteria, including Pseudomonas, Staphylococcus, and Escherichia coli. The goal is to develop “designer phages” capable of infecting a wide range of bacterial strains, a departure from previous methods that relied on standard treatments.
Pogliano emphasizes the need for a tailored approach, stating, “You can’t just pick any phage off the shelf and throw it on any bacteria as we did with penicillin.” The research team is committed to bioengineering phages with genetic payloads that can deliver therapeutics directly to infected patients, enhancing the efficacy of phage therapy.
The developments at UC San Diego align with the efforts of the Center for Innovative Phage Applications and Therapeutics, the first dedicated phage therapy center in the United States. This center focuses on translating research findings into clinical applications aimed at treating persistent bacterial infections.
As the battle between bacteria and viruses intensifies, the promising potential of jumbo phages may herald a new era in the fight against drug-resistant infections, offering hope for effective treatments where traditional antibiotics have failed.
