Barr Lab

Research Areas

Phage Therapy

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?

My name is Fernando Gordillo-Altamirano, I am a Medical Doctor from Ecuador and a PhD student at the Barr Lab. With my project –Bacteriophage adjuvant therapy against multidrug-resistant Acinetobacter baumannii infections– I plan to elucidate the mechanisms through which phages and antibiotics can work together against one of the most problematic hospital pathogens. It has been recently observed that bacteria that evolve to become resistant to phages attain certain associated fitness costs. Consequences of phage-resistance on the bacterial cells include impaired growth, reduced virulence, or even re-sensitisation to antibiotics. These are the observations upon which I am basing my research.

At the Barr Lab, we are establishing a library of phages against bacterial pathogens and I have already incorporated 9 phages with lytic activity against a set of 8 A. baumannii strains. I have also created phage-resistant A. baumannii mutants. By comparing the wild type and phage-resistant strains with several assays, including phenotypic and genotypic approaches, I will identify the mechanistic trade-offs of bacterial phage resistance. My methods include the analysis of bacterial growth curves, antibiotic susceptibility profiling, competitive fitness assays, quantification of biofilm and virulence factor production, whole genome sequencing, and proteomics. The in vitro results of the project will guide in vivo experiments in animal models of A. baumannii infection.

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.

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Monash University
School of Biological Sciences
Senior Zoology
Clayton VIC 3168

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