Canine Pseudomonas aeruginosa infections

17 September 2024

In 2022, Dr Gavin Paterson from the University of Edinburgh received BSAVA PetSavers funding for a master’s degree by research investigating the potential of phage therapy to tackle Pseudomonas aeruginosa infections in dogs. Student Shannon Street tells us more…

From the beginning of my veterinary degree, I had always been interested in the field of scientific research and especially where the research outcomes have potential impacts at a clinical level. A specific area that I always considered very important was research into antimicrobial resistance and the search for alternative therapeutics. When I came across this PetSavers- funded 12-month MScR project about phage therapy, I knew I had to apply and was so grateful when my application was successful. This project allowed me to get a taste of the world of postgraduate research and it would not have been possible without the support of PetSavers. For any other veterinary surgeon who is considering a career in scientific research, I would highly recommend applying for a PetSavers grant-funded project.

Background and aims of the project

Pseudomonas aeruginosa is an opportunistic bacterial pathogen in both human and veterinary medicine. Infections tend to be very difficult to treat due to high rates of antimicrobial resistance. Pseudomonas otitis is a common condition seen in canine veterinary practice and is often viewed as one of the most challenging ear infections to treat. The infections frequently do not respond to conventional antibiotics and, in severe cases, vet surgeons may even have to resort to total ear canal ablation surgery. A novel approach to the treatment of P. aeruginosa infections is therefore needed to improve animal welfare. Bacteriophages (often referred to as ‘phages’) are bacterial viruses that are ubiquitous in the environment. Phage therapy involves harnessing the bacterial killing capabilities of phages and utilizing these to fight bacterial infections. Though phage therapy is a growing area of research, it has not yet been fully exploited in companion animal vet practice. Dr Gavin Paterson, alongside Professor David Gally and Professor Tim Nuttall, at the University of Edinburgh, wanted to investigate the potential of phage therapy as a treatment of canine otitis associated with P. aeruginosa. The aims of the project were to isolate appropriate phages capable of killing canine otitis isolates of P. aeruginosa and then characterizing said phages.

Results of the project

Five phages with potential as phage therapy candidates were isolated from wastewater samples obtained from around Scotland. These were then characterized in the following ways:

■ Imaging of the phage particles using transmission electron microscopy (Figure 1)

■ Assessment of bacterial host ranges by testing the phage killing capabilities with 24 canine otitis P. aeruginosa isolates

■ Assessment of the ability of the phages to inhibit biofilm formation of canine otitis P. aeruginosa isolates

■ Phage genome sequencing to assess the genetic content of the phages.

Overall, although the phages had some beneficial qualities as phage therapy candidates, their limited host ranges (i.e. they could only kill a few P. aeruginosa strains) restrict their potential use in phage therapy. However, further research could find ways to combat this, including training the phages using a variety of laboratory-based techniques to increase their host range. Also, using these phages in conjunction with other phages that target different P. aeruginosa canine otitis strains in one treatment dose (termed a ‘phage cocktail’) is another possibility.

Challenges and obstacles of the project

There were a few obstacles in the laboratory-based segment of my project, predominantly at the beginning! It was assumed that appropriate phages would be isolated from the wastewater samples with relative ease, due to the ubiquity of phages. However, this step proved trickier than initially predicted and it took several months to find phages. As a result, there was less time than desired to characterize them fully. Despite this, as with all obstacles in a research project, there were positives to come from this difficulty. It allowed me to work methodically through the issue to come up with solutions and provided even more satisfaction when I finally found phages! Furthermore, the difficulty itself tells us something about the world of phages, which is that we still do not understand them fully.

Highlights and relevance for clinical practice

Phages that had killing capabilities against some P. aeruginosa canine otitis isolates were successfully isolated in this project. With some further research and phage candidates, there is potential for this to result in a phage therapy treatment that could be available in clinical practice. This would likely be a topical treatment to apply to the ear canal, possibly in conjunction with antibiotics. This could help clear stubborn P. aeruginosa infections and potentially inhibit the development of further antibiotic resistance by sparing antibiotic use.

FIGURE 1: Representative images of two phage particles isolated during this project using a transmission electron microscopy (Model JEOL JEM-1400 Plus) and formatted using ImageJ software.

 

About the author

Shannon Street graduated from the Royal (Dick) School of Veterinary Studies in 2020. During her veterinary degree, she also completed an intercalation BSc (Hons) in Infectious Disease. After spending 2 years in small animal clinical practice, she returned to the University of Edinburgh to complete a PetSavers-funded MScR, predominantly based at the Roslin Institute.

 

Supporting more BSAVA PetSavers research

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