Abstract
Individuals with cystic fibrosis (CF) are given antimicrobials as prophylaxis against bacterial lung infection, which contributes to the growing emergence of multidrug resistant (MDR) pathogens isolated. Pathogens such as Pseudomonas aeruginosa that are commonly isolated from individuals with CF are armed with an arsenal of protective and virulence mechanisms, complicating eradication and treatment strategies. While translation of phage therapy into standard care for CF has been explored, challenges such as the lack of an appropriate animal model demonstrating safety in vivo exist. In this review, we have discussed and provided some insights in the use of primary airway epithelial cells to represent the mucoenvironment of the CF lungs to demonstrate safety and efficacy of phage therapy. The combination of phage therapy and antimicrobials is gaining attention and has the potential to delay the onset of MDR infections. It is evident that efforts to translate phage therapy into standard clinical practice have gained traction in the past 5 years. Ultimately, collaboration, transparency in data publications and standardized policies are needed for clinical translation.
Highlights
Cystic Fibrosis (CF) is a life-limiting genetic disease caused by mutations to the Cystic Fibrosis Transmembrane Regulator (CFTR) gene
The genetic defect leads to impaired water and electrolyte traffic of airway epithelial cells (AECs), tenacious airway surface liquid, impaired mucociliary clearance
Translational Potential of Bacteriophage mucus build-up in the lungs of those afflicted due to the inability of AECs to allow chloride ions to pass into the airway surface liquid (Crawford et al, 1991; Haq et al, 2016)
Summary
Cystic Fibrosis (CF) is a life-limiting genetic disease caused by mutations to the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. Successful use of phage therapy in CF has been reported, this has been approved on compassionate grounds and its translation into standard clinical care still requires additional rigorous, systematic and detailed exploration (Supplementary Table 1). The first reported compassionate use of phage therapy in CF was for a 15-year old patient with disseminated Mab infection at sites other than the lung following bilateral lung transplant (Dedrick et al, 2019; Figure 1).
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