Current research in immune diseases, infectious diseases and antimicrobial resistance

 

Placing a blood sample onto a petri dish

Comparison of serum procalcitonin and serum amyloid A (SAA) concentrations as a marker of bacterial causes of systemic inflammatory response syndrome (SIRS) in cats

Student Research Project Grant: £3200 awarded in 2023

Institution: University of Cambridge

Lead researcher: Tim Williams

Serum procalcitonin concentrations are higher in cats with bacterial causes of sepsis (systemic inflammatory response syndrome, SIRS) than in those with other causes.

Aim: This undergraduate project will explore the prognostic value of procalcitonin in cats with bacterial SIRS and its correlation with serum amyloid A concentrations, which is another biomarker of systemic inflammation. This will hopefully provide an objective way to predict prognosis and identify bacterial causes of SIRS in cats, thus aiding treatment decisions.

 

Reusable vs disposable drapes: does their use affect post-operative wound complication rates in routine surgeries?

Clinical Research Project Grant: £9,053 awarded in 2022

Institution: Vet Partners, York

Lead researcher: Hannah James

The use of reusable surgical drapes instead of disposables is frequently recommended to reduce waste volumes and environmental impacts in veterinary practice. The choice of doing so for veterinary practices may depend on factors including cost, convenience and practitioner preference, with both types of drape in common usage. There is no clear evidence as to whether either is preferable in terms of post-operative infections or other wound complications.

Aim: This study hopes to identify whether there are measurable differences in wound healing attributable to the choice of drape, to enable practitioners to factor this into their choice.

 

Acute phase protein and micro RNA signatures for the diagnosis and prognosis of feline infectious peritonitis

Master’s Degree by Research Grant: £39,865 awarded in 2022

Institution: University of Edinburgh

Lead researcher: Danielle Gunn-Moore

Feline infectious peritonitis (FIP) results in inflammation of the blood vessels throughout the body, and affects 5-10% of pet cats. Its cause is poorly understood, it is difficult to diagnose and until recently it responded poorly to all treatments.

Aim: This master’s degree will investigate the role of acute phase protein profiles in FPP and explore the potential of micro-RNA signatures, which may prove to be a sensitive new test.

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The susceptibility of Staphylococcus pseudintermedius to fluoroquinolones and their suitability for treating infections with methicillin resistant Staphylococcus pseudintermedius (MRSP): a pilot study

Clinical Research Project Grant: £5818.71 awarded in 2021

Institution: University of Liverpool

Lead researcher: Nicola Williams

Staphylococcus pseudintermedius is the main coagulase-positive, Gram-positive mucosal commensal bacteria in dogs. Methicillin-resistant S. pseudintermedius (MRSP) carries the mecA gene, and such bacteria are often also multidrug resistant. Treatment of MRSP infections is challenging due to a lack of treatment options, and inappropriate therapy may result in treatment failure and poor welfare.

Aim: This study aims to investigate the susceptibility of a cross section of S. pseudintermedius to fluoroquinolones and to assess whether exposure of these bacteria to the drugs may select for resistance. These data will further inform both whether these drugs are likely to be effective and appropriate for treating such infections.

 


Past research in this area

 

Evaluation of antimicrobial activity of canine urinary extracellular vesicles against causative agents of canine otitis externa (Pseudomonas aeruginosa and Staphylococcus intermedius)

Student Research Project Grant: £3180 awarded in 2023

Institution: University of Cambridge

Lead researcher: Tim Williams

Bacterial species that cause canine otitis externa are becoming increasingly antibiotic resistant.

Take home message: This undergraduate project demonstrated the significant antimicrobial activity of canine urinary extracellular vesicle preparations against P. aeruginosa and S. intermedius, suggesting they could provide a novel topical therapeutic against these species.

Findings were presented as an abstract at BSAVA Congress 2024, which can be freely accessed here.

 

Comparing the early viral entry process in avirulent and virulent caliciviruses

Student Research Project Grant: £2600 awarded in 2023

Institution: University of Glasgow

Lead researcher: Margaret Hosie

Caliciviruses cause diseases of global importance to human and veterinary medicine. Although vaccines are available for feline calcivirus, virulent strains have emerged that can cause severe disease.

Take home message: This undergraduate study used cryo-electron microscopy to obtain a high-resolution structure of respiratory feline calicivirus strain FCV 273 to a resolution of 2.7-Å, revealing stable P2 domains and laying the foundations for effective vaccine development.

Findings were presented as an abstract at BSAVA Congress 2024, which can be freely accessed here.

 

Investigating the potential of phage therapy to tackle Pseudomonas aeruginosa infections in dogs

Master’s Degree by Research Grant: £9,053 awarded in 2022

Institution: University of Edinburgh

Lead researcher: Gavin Paterson

Pseudomonas aeruginosa is an important cause of chronic otitis in canine veterinary practice and infections are often very difficult to treat due to antimicrobial resistance. Phage therapy, using bacterial viruses to kill pathogenic bacteria, is a possible therapeutic approach. This master’s degree isolated five novel lytic phages with potential as phage therapy candidates from wastewater samples. These were characterised by imaging, genome sequencing and the testing of their phage killing capabilities.

Take home message: The novel phages showed activity against canine otitis isolates of P. aeruginosa, although their host ranges were somewhat limited. However, these could be improved by phage training or they could be used in conjunction with other phages, thus offering potential for new treatments against pathogenic bacteria.

 

Characterising the virus neutralising antibody response to SARS-CoV-2 in the UK feline population and examining changes in seroprevalence during the different phases of the pandemic

Student Research Project Grant: £2771 awarded in 2022

Institution: University of Glasgow

Lead researcher: Margaret Hosie

This undergraduate project assessed the ability of sera from domestic cats to neutralise four SARS-CoV-2 pseudotypes (B.1, Alpha, Delta, and Omicron (BA.1)) to characterize feline virus neutralising antibody responses in the UK. Pseudotype-based neutralisation assays were performed on residual serum samples collected from 806 domestic cats and seropositivity was confirmed using a double antigen bridging immunoassay.

In Spring-Summer 2022, feline anti-SARS-CoV-2 seroprevalence was shown to decline to 4%. Neutralising antibody titres were highest against B.1 and Delta pseudotypes and lowest against Omicron. Seropositive cats developed a neutralising antibody titre against one or more SARS-CoV-2 variants, but the degree of cross-neutralisation varied between individuals. Likelihood of seropositivity was not associated with sex, age, or pedigree of cats. The recent decline in neutralising antibody titres and the significantly weaker response against Omicron suggest that previously infected cats may be vulnerable to reinfection when exposed to newer SARS-CoV-2 variants.

Take home message: Adopting a One-Health strategy that involves monitoring both humans and their pets could be pivotal in helping control the COVID-19 pandemic, particularly recognising concerns about infections spilling back to humans.

Findings were presented as an abstract at BSAVA Congress 2023, which can be freely accessed here.

 

What is the role of urinary extracellular vesicles in the pathogenesis of canine urinary tract infection and asymptomatic bacteriuria? 

Student Research Project Grant: £2500 awarded in 2021

Institution: University of Cambridge

Lead researcher: Tim Williams

Urine infections are relatively common in dogs, but the cause of these infections is often unclear. This undergraduate project investigated the bactericidal properties of urinary extracellular vesicles (UEVs) in dogs with and without bacteriuria.

Take home message: Canine UEV preparations demonstrated antimicrobial activity at physiologically relevant concentrations, although the potency of UEV antimicrobial activity was variable between individuals.

Findings were presented as an abstract at BSAVA Congress 2023, which can be freely accessed here.

 

Cotton wool versus non-woven gauze swabs: comparatively which is more efficacious for minimising the preoperative microbial load on the ovariohysterectomy surgical site in bitches?

Student Research Project Grant: £2050 awarded in 2021

Institution: Harper Adams University

Lead researcher: Kat Holt

Surgical site infections are a common complication of veterinary surgeries, and are mainly caused by commensal bacteria such as Staphylococcus pseudintermedius. The antiseptic agent and application technique have been recognised and researched as two key components of surgical skin preparation, but less is known about the material utilised to apply the antiseptic solution. This undergraduate project investigated the clinical efficacy of cotton wool versus non-woven gauze swabs for reducing microbial contamination of the ovariohysterectomy surgical site in bitches pre-operatively.

The skin microbiome on the bitch ovariohysterectomy surgical site in dogs (n=24) undergoing ovariohysterectomy was sampled pre- and post-antisepsis following randomisation to an antisepsis protocol of 4% chlorhexidine gluconate and either cotton wool (n=12) or non-woven gauze swabs (n=12).

Take home message: There was no significant difference between cotton wool and non-woven gauze for microbial reduction nor for post-operative licking of the surgical site, indicating that both materials are equally efficacious.

 

Pathogens and antimicrobial resistance in raw meat diets for dogs

Student Research Project Grant: £2500 awarded in 2020

Institution: University of Liverpool

Lead researcher: Gina Pinchbeck

Raw meat and bone (RMB) diets for dogs are increasing in popularity in the UK. Previous studies have shown that they can be contaminated with E. coli and Salmonella species of bacteria, and that feeding these diets is a risk factor for the detection of canine faecal antimicrobial-resistant (AMR) bacteria. This undergraduate study determined the types and sources of RMB diets being fed to dogs, the prevalence of E. coli and Salmonella present, and the types of plasmids and associated resistance genes present on them in this food.

A total of 190 faecal samples were collected from dogs from 140 households (114 samples from raw-fed dogs and 76 from non-raw-fed dogs). Salmonella species were detected in four percent of the samples (all raw-fed) and AMR E. coli was detected in 62 percent of raw-fed dogs with only 13 percent of non-raw-fed dogs.

Take home message: Statistical analysis confirmed that dogs fed raw food diets had 7.5 times the odds of having MDR (multi-drug resistant), more than 14.5 times the odds of having 3GCR (third generation cephalosporin-resistant), and more than 6 times the odds of having AMR (resistance to at least one tested antimicrobial) E. coli in their faeces than dogs fed non-raw diets.

This work was published in the June 2022 issue of the Journal of Small Animal Practice, and this article won the BSAVA PetSavers Veterinary Achievement Award in 2022. Our press release on the study can be accessed here.

 

Can we use bacterial outer membrane vesicles as a novel anti-bacterial therapy?

Student Research Project Grant: £2500 awarded in 2020

Institution: University of Cambridge

Lead researcher: Tim Williams

Outer membrane vesicles from a variety of bacterial strains, including E. coli, have bacteriolytic effects against other bacteria including P. aeruginosa which is a common bacterial isolate in canine otitis externa. The treatment of P. aeruginosa otitis is challenging because many strains are resistant to numerous antimicrobials.

Take home message: This undergraduate project found that bacterial outer membrane vesicles derived from BL21 strains of E. coli were not universally bactericidal, although there was some evidence of bactericidal activity against one isolate of P. aeruginosa.