Project information
Interactions between therapeutic staphylococcal phages and their hosts in bacterial communities and consequences for phage-antibiotic synergy (PAS)

As Staphylococcus aureus is becoming more resistant to antibiotics, new antimicrobials are urgently required and phage therapy should be considered. Phages are more specific than antibiotics, do not harm commensal microbiota, modulate immunity in vivo and can degrade biofilms. Although phage-resistant strains are emerging, the high frequency of mutations and polymorphism allows phages to naturally overcome the resistance by coevolving more infective. Under laboratory conditions, the infectivity of phages to a given host can be further increased by repeated propagation through experimental evolution, i.e., phage training. Moreover, the efficacy of clinical antibiotics can be improved via phage-antibiotic synergy (PAS), as phages can re-sensitize resistant strains to antibiotics. Several studies have addressed PAS, usually focusing on effective combinations or mechanisms of action. However, approaches that use phage training to increase the efficacy of PAS are lacking. Moreover, PAS is often studied on monocultures instead of bacterial communities that are more typical for clinical infections. The aim of the internship is to set up a new approach to use experimental evolution to increase the efficacy of PAS in polymicrobial communities in Friman lab. Proximate mechanisms will be studied by exploring genomic changes in pathogens and their phages, focusing on long-read sequencing pipelines. Results will be published in a scientific journal and used for a joint grant proposal to continue collaboration in the future.