PetSavers – BSAVA PetSavers supporting antimicrobial resistance research
7 September 2021
My first degree was at Edinburgh University, where I graduated with a first-class honours degree in Medical Microbiology in 1999. Growing up near Edinburgh in the 1980s I became aware of microbiology at an early age due to media coverage of the HIV crisis in the city at that time. I remember there being a massive public health campaign and lots of concern and worry for people during the emergence of AIDS. My child’s mind was amazed that something so tiny, too small to see even, could actually be so deadly and so feared; people, after all, were big and powerful with tanks and armies to defend themselves! My intrigue was married to a degree of worry; if you can’t see microbes how you can stop them?! So, spurred by that early curiosity and perhaps a slight hint of germaphobia, I was set at a young age on a career in microbiology.
I then headed west to Glasgow University for a PhD on their Wellcome Trust 4-year PhD programme ‘Molecular Mechanisms of Disease’. My PhD research investigated virulence factors and the disease pathogenesis of the bacterial pathogen Streptococcus pneumoniae (the pneumococcus). At that time in the early 2000s, there was great excitement in the field due to publication of the first pneumococcal genome sequence in the prestigious journal Science. Bacterial genome sequencing has become infinitely more accessible since then, becoming a standard research tool as well as emerging in diagnostic laboratories. For instance, there are now almost 100,000 sequenced S. pneumoniae genomes in public databases and sequencing a single isolate today would not get you a paper in Science, unfortunately. That gave me an early insight into the power of genomics to understand bacteria better and this is something that I continue to be interested in.
Following my PhD, I continued research on various bacterial pathogens as a postdoctoral researcher at Glasgow University, the Ministry of Defence at Porton Down, the University of Texas, Oxford University and Cambridge vet school. It was during two productive and enjoyable spells at Cambridge, working with Professor Duncan Maskell on Salmonella enterica and Professor Mark Holmes on Staphylococcus aureus, that I become interested in veterinary microbiology and the interface between humans and animals in relation to pathogens and antimicrobial resistance. These are research themes that have stayed with me in my position at the Dick Vet where I have been since 2016.
The PetSavers project I supervised was a collaboration with Dr Tim Nuttall, Head of Dermatology at the Dick Vet, and veterinary dermatologist Dr Katarina Varjonen, formerly of the Dick Vet and now based in Sweden. The project began in July 2019 when student Logan Newstead joined the Dick Vet after receiving a First Class BSc (Hons) in Bioveterinary Science from the University of Lincoln.
As with many bacterial pathogens, antimicrobial resistance is a growing concern with Staphylococcus pseudintermedius, a common cause of canine pyoderma, with many isolates becoming difficult to treat because of multidrug resistance. Our Master’s project therefore set out to identify new, alternative antimicrobials that are active against S. pseudintermedius and which could be used as an adjuvant or replacement treatment to help preserve the utility of current antimicrobials.
The approach we used was to identify and characterise bacteriocins from the healthy dog microflora that are inhibitory against S. pseudintermedius. Bacteriocins are antimicrobial peptides produced by many, if not most, bacterial species which kill closely related strains and species. They are likely to play an important ecological role during interspecies competition and may be one way in which the normal healthy-state microbiome can help protect against colonisation and infection by pathogenic organisms. Indeed, in the case of canine pyoderma, there is evidence that a dysbiosis of the normal skin microbiome contributes to disease pathogenesis and S. pseudintermedius infection.
The use of bacteriocins as alternative antimicrobials has received growing attention, with several being exploited as food preservatives and being granted ‘generally regarded as safe’ (GRAS) status. Bacteriocins have several potential advantages over traditional antimicrobials, such as having a very narrow spectrum of activity which results in less disruption to the microbiome and a reduced selective pressure for the development of resistance. They are also amenable to bioengineering as a way of enhancing their properties, are active at very low concentrations and function against antibiotic-resistant strains.
Our project isolated bacteria from the skin microbiome of over 100 healthy dogs and screened these for inhibitory activity against clinical isolates of S. pseudintermedius. We used an agar diffusion method, similar to disc diffusion used for antimicrobial sensitivity testing, to obtain a number of ‘hits’ representing isolates capable of inhibiting S. pseudintermedius growth in the laboratory. These inhibitory isolates were studied further to test if they had activity against a broad range of genome-sequenced, unrelated S. pseudintermedius isolates that are reflective of those causing infections. We also tested our inhibitory isolates for activity against Staphylococcus aureus and Staphylococcus schleiferi, which are two other important pathogenic staphylococci in dogs. The inhibitory isolates have had their genomes sequenced to identify their bacteriocins genes, and two of our isolates are new species of bacteria which is very exciting! The strains and bacteriocins we have found may lay the foundation for much-needed new antibiotics to help tackle S. pseudintermedius infections, and several are active against multidrug-resistant isolates.
The COVID-19 pandemic and lockdown caused some disruption to our plans, but the project has been completed successfully. In that regard, we are particularly grateful to PetSavers for their flexibility around the award that allowed us to mitigate the negative impact of COVID-19 as much as possible. Indeed, we are grateful for their generous support in the first place, without which we just would not have been able to undertake the amount of work involved. So far, we have published two manuscripts (https://www.mdpi.com/2079-6382/9/2/40/htm and https://www.microbiologyresearch.org/content/journal/ijsem/10.1099/ijsem.0.004878#tab2), and, very importantly, Logan successfully passed her Master’s examination, being awarded a distinction for her excellent work.