Mukesh Varshney

Patients with cystic fibrosis are at risk of developing infections caused by Pseudomonas aeruginosa. Normally, these infections are challenging to treat and require intravenous treatment for two weeks. Moreover, the patients frequently remain colonized with P. aeruginosa and with time the strains accumulate antimicrobial resistance mechanisms, thus compromising future treatment. Despite recent emergence of novel antimicrobials, development of resistance is observed already before the new antimicrobials are introduced on the market. Novel strategies are urgently needed for the management of these infections, and it has been proposed to combine traditional antimicrobials with bacteriophages, viruses that selectively infect and kill bacteria with very high specificity. Herein, we describe a multidisciplinary approach with isolation and characterization of bacteriophages and evaluation of their properties in lung organoid models, murine pneumonia models, and finally in a clinical trial where combination of bacteriophages and antimicrobials is compared to standard of care treatment. The infection models described herein simulate acute-on-chronic infections, and we will use multi-omics strategies to assess the immune responses. Phages that will be used in the project have largely been isolated and their detailed bioinformatical characterization is ongoing. Discussions are also ongoing with regulatory agencies on clinical trial design to allow for rapid clinical translation.