Results from a recent Dartmouth-led study, with partners from the University of Pittsburgh and Yale University and reported in the journal PLOS Biology, offer new insights into the potential of bacteriophage (phage) therapy to treat diseases such as cystic fibrosis (CF). CF is an inherited disease that causes thick mucus to build up, posing a significant treatment challenge.The disease causes persistent infections in the lungs, which can result in respiratory failure and death. According to Jennifer Bomberger, PhD, a professor of microbiology and immunology at Dartmouth’s Geisel School of Medicine, opportunistic pathogens such as Pseudomonas aeruginosa, have become increasingly resistant to antibiotics. This has led to the need for new and creative ways to treat these infections. Phage therapy, developed many decades ago, has been successful in Eastern Europe and is being considered as a potential treatment option.”Phage therapy is becoming increasingly utilized in clinical trials and compassionate use cases through Emergency Use Authorizations in the U.S. for treating difficult-to-treat infections,” according to Paula Zamora, PhD, a postdoctoral associate at Geisel and the primary author of the study.
Zamora also explains that one of the benefits of phage therapy, which involves using viruses to eliminate bacteria, is that it does not require repeated administration like antibiotics. Instead, it has a self-amplification mechanism where phages replicate by attaching to bacteria and injecting their genetic material. As more phages are produced, more bacteria are killed.
Phage therapy is an innovative approach for treating infections and is increasingly being used in clinical trials and compassionate use cases through Emergency Use Authorizations in the U.S.,” says Paula Zamora, PhD, a postdoctoral associate at Geisel and first author on the study.
One of the advantages of phage therapy, which uses viruses to kill bacteria, “is that unlike antibiotics which need to be given repeatedly, it has this mechanism of self-amplification,” Zamora continues. “Phages are able to replicate by binding to bacteria and injecting their genetic material — as phages make more phages, they kill more bacteria.”
While phage therapIt is believed that phage therapy is relatively safe and has few side effects, but there are still important gaps in our understanding of how phages interact with the cells of the human respiratory tract. “Since very high doses of phages are often needed to have a therapeutic effect, we wondered, ‘Do the host cells detect these phages, and do they create an inflammatory response that we should be concerned about?'” says Bomberger. To investigate this, the researchers collaborated with scientists at Pitt and Yale to study interactions between a group of Pseudomonas aeruginosa phages with therapeutic potential.Potential and human airway epithelial cells derived from a person with CF and grown in cell lines in the lab. The study found that respiratory epithelial cells react to therapeutic phages, and that the interactions between phages and epithelial cells are diverse and depend on specific phage properties and physiochemical features of the airway microenvironment. Zamora also mentioned that their research suggests that immune responses to phages could be used to enhance the effectiveness of phage therapy on an individual level, hoping that their findings will lead to further studies in this area.The impact of phages on the human body is being investigated. Phage therapy design does not currently require the evaluation of phage effects on human cells. Bomberger suggests that as phages are being screened for their ability to kill bacteria, it is also important to consider the immune responses they may trigger in the host. This information should be taken into account when selecting which phage to use in treating a patient.
