Identification of vaccine targets for Streptococcus suis infection in humans and pigs

Streptococcus suis (S. suis) is responsible for significant mortality and morbidity in pig production, affecting economics, animal welfare and food security within commercial and small scale farming worldwide and manifests as meningitis, septicaemia and polyarthritis in piglets and joint diseases in adult pigs. It is also an emerging zoonotic pathogen with the highest prevalence in Southeast Asia, with septicaemia and meningitis common clinical progressions in humans, with up to 40% of bacterial meningitis cases in Vietnam. Whilst treatment with beta-lactam based antibiotics can resolve disease, reports of multiple drug resistant strains are increasing and the OIE has identified S. suis as a priority disease for which vaccines could significantly reduce the use of antimicrobials in animals and therefore decreasing pressure on generation of antimicrobial resistance. The overall aim of this study is to identify components for protective vaccine and diagnostic test development for more effective disease control of S. suis infection in both humans and pigs. This studentship will characterise genes/proteins essential for pathogenesis in whole blood using a combination of random mutagenesis and high throughput sequencing, using our existing bacterial mutant pools using the pGh9:ISS1 insertional mutagenesis system, and a bespoke laboratory and bioinformatic analysis programme called PIMMS which identifies conditionally important/essential sequences that will be translated to metabolic pathways and biochemical processes for further comparative analysis. Bacterial mutants will be screened for their ability to survive in whole pig and human blood to determine a list of genes are essential for survival and therefore a direct target for control of infection. Knockout individual bacterial mutants of several surface associated genes will be isolated using existing PCR screening methods and recombinant versions generated for antiserum production, immunoreactivity and bacterial growth inhibition testing as proof of concept experiments for vaccination and diagnostic test development.