Inhaled phage therapy

Bacteriophages to combat bacterial infections in the lungs

Phages are nano-sized viruses that can only infect and replicate inside the bacterial hosts. They are considered safe, unaffected by antibiotic resistance and are able to penetrate the biofilm, replicating locally to kill bacteria.

TEM image of phage — Transmission electron microscopy (TEM) image of anti-pseudomonas myovirus phage PEV61

A major interest of our group is using bacteriophages (phages) to combat bacterial infections in the lungs caused by multidrug resistant (MDR) bacteria. Our work is focused on developing stable dry powder phage formulations and establishing PK/PD profiling as well as uncovering the phage stabilisation mechanisms.

The World Health Organization has identified antimicrobial resistance as one of the three greatest threats to human health with S. aureus and P. aeruginosa among the 6 top-priority dangerous ESKAPE ‘superbugs’ identified by IDSA as requiring the most urgent attention for discovery of novel therapeutics. The purpose of this project is to develop novel therapeutics using phages to address the major clinical problem associated with infections caused by MDR pathogens.

SEM image of powders containing phage — Scanning electron microscope (SEM) image of spray dried inhalable powders containing phage PEV61

We have produced novel phage-containing powders that provide biological and physicochemical stability, and are suitable for inhalation delivery.^1-3 A recent proof-of-concept efficacy study showed extremely efficacious properties of our novel formulations in vivo, laying foundations for further exploring inhaled phage therapy as a treatment option for lung infection caused by MDR pathogens. We are also studying antibiotic and phage combination treatment against planktonic cells and biofilms. Furthermore, we are delving into mechanistic studies to uncover phage stabilisation mechanism in powder formulation using nanoIR spectroscopy (in collaboration with the Sydney Nano theme leader Dr Wojtek Chrzanowski). This project will lead to an economic and efficient technology to produce phage aerosols for novel treatment strategies of infections by inhalation.

This project is supported by the Australian Research Council and National Institute of Allergy and Infectious Diseases within the National Institutes of Health.