Shortly after the discovery of phages, scientists and physicians realised their therapeutic potential. Phage therapy is the direct administration of lytic phages to a patient with the purpose of killing the bacterial pathogen that is causing a clinically relevant infection. During the pre-antibiotic era, great interest arose around phage therapy. Then Alexander Fleming discovered penicillin in 1928.

Not even a century has passed since the discovery of antibiotics. However, it is difficult to imagine life without them. Antibiotic therapy has saved millions of lives and has been pivotal for medical breakthroughs such as organ transplantation and cancer chemotherapy. The possibility of losing antibiotic therapy as a resource in healthcare is truly frightening. But it is happening. Antibiotic resistance is a naturally-occurring event. Bacteria can be intrinsically resistant to one or more antibiotics, but can also acquire resistance traits through numerous mechanisms. Furthermore, human activity –especially antibiotic overuse– greatly accelerates the processes driving antibiotic resistance. Add in the factor of a dry pipeline in antibiotic research and development, and we have the reasons behind the “post-antibiotic era” we are quickly approaching.

 Given these circumstances, it is unsurprising that interest towards phage therapy has been rekindled. Throughout the world, great work is being done to establish the effectiveness and safety of phage therapy. Recently, we were part of the team involved in the first case report of successful intravenous phage therapy in the United States (read the press release from Washington Post and Time Magazine, with the published paper here). The significance of that work was highlighted as it not only proved the usefulness of phage therapy as an alternative to antibiotics, but the potential use of phages and antibiotics combined.

In Pharmacology, the combined effect of two –or more– therapeutic agents can sometimes be greater than the sum of their individual effects. This phenomenon is known as synergy, and brings about significantly higher rates of treatment success. Could it be possible to achieve synergy when combining phages and antibiotics to treat bacterial infections?

At the Barr Lab, we are establishing a library of phages against a panel of diverse, clinically-relevant, and antibiotic-resistant bacterial pathogens. We characterise the fundamental biology of phages infecting these hosts to gain new insights that we may be able to exploit clinically. By comparing the wild-type and phage-resistant strains with several assays, including phenotypic and genotypic approaches, we can identify phage receptors and the mechanistic trade-offs of bacterial phage resistance. 

We are exploring the field of phage research from the biological, evolutionary, and clinical points of view. Our ultimate goal with this project is to provide strong evidence to support advancements towards the standardisation and reasonable use of phage-antibiotic combination therapy. After all, two is better than one.