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In a new study published in the journal PLOS Biology, researchers from Dartmouth, the University of Pittsburgh, and Yale University investigated the therapeutic potential of bacteriophages (phages) for treating diseases like cystic fibrosis (CF). CF is a genetic disease that causes thick mucus to accumulate in the lungs, leading to persistent infections that can be difficult to treat. One of the pathogens commonly associated with CF, Pseudomonas aeruginosa, has become increasingly resistant to antibiotics, prompting the need for alternative treatment options.

Phage therapy, which uses viruses to kill bacteria, has shown promise in treating difficult-to-treat infections and is being used in clinical trials and compassionate use cases. Unlike antibiotics, which typically need to be given repeatedly, phages have the ability to self-amplify by replicating and killing more bacteria. The safety profile of phage therapy is relatively good with few side effects, but there are gaps in knowledge regarding how phages interact with human respiratory tract cells, particularly in individuals with CF.

The researchers sought to address these knowledge gaps by studying interactions between a panel of Pseudomonas aeruginosa phages and human airway epithelial cells derived from a person with CF. They found that respiratory epithelial cells do sense and respond to therapeutic phages, and that these interactions are dependent on specific properties of the phages as well as the microenvironment of the airway. Additionally, the study suggested that immune responses to phages could potentially be harnessed to improve the effectiveness of phage therapy on an individual basis.

The study highlights the importance of considering the effects of phages on human cells when designing phage therapy. Currently, evaluations of phage therapy design typically focus on the ability of phages to kill bacteria, with less emphasis on their effects on the human host. The researchers suggest that understanding the immune responses elicited by phages could play a role in selecting the most appropriate phage for treating individual patients. By incorporating immune response data into the decision-making process, healthcare providers may be able to optimize the effectiveness of phage therapy for treating resistant infections in diseases like CF.

Overall, the study provides valuable insights into the potential of phage therapy for treating diseases like cystic fibrosis. By shedding light on the interactions between phages and human respiratory epithelial cells, the research opens up new possibilities for optimizing phage therapy and improving outcomes for patients with difficult-to-treat infections. Further studies are needed to explore the effects of phages on the human host and to better understand how immune responses can be leveraged to enhance the efficacy of phage therapy on an individual basis.

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