Abstracts (first author)
Phage therapy might not help everyone; bacterial resistance and phage infectivity evolution considerably varies between different Cystic Fibrosis patients
Phage therapy, the use of viruses to specifically kill only the disease-causing bacteria, could offer an alternative way to fight against antibiotic resistant bacteria. Even though phage selection could lead to increased bacterial resistance, phage therapy has the potential to become an evolutionary sustainable medicine: phages can coevolve more infective and thus retain their efficiency to keep bacteria under control. Here we studied experimentally in vitro the long-term coevolutionary dynamics of model phage therapy by using four natural phage species and Pseudomonas aeruginosa bacterial strains isolated from the lungs of ten Cystic Fibrosis patients. We found that bacteria and phages coevolved during the three weeks of cocultivation. However, coevolution was asymmetric by favouring bacterial resistance over phage infectivity, which suggests that phages might not be able to overcome bacterial resistance evolution indefinitely. When ancestral and coevolved phages were applied continuously to ancestral bacterial cultures, coevolved phages were clearly more efficient in reducing bacterial densities with lower corresponding increase in bacterial resistance. These results demonstrate that environmentally derived phages could be used to eradicate clinical bacterial infections, while the effectiveness of phage therapy could be enhanced by coevolving phages more infective in vitro. Despite this potential, our study also shows an important caveat: phages’ ability to reduce bacterial densities varied considerably between different patients having very large to negligible effects. As a result, phage therapy is unlikely to work uniformly across all patients and might need to be adjusted case-specifically according to given host and parasite genotypes. Recognising between-patient variation in bacteria-phage coevolution is thus crucial for developing a broad-spectrum phage therapy, which is effective against multiple pathogen genotypes.