Project Reference: TRG27-VET-LW1

Project title: Evolving to Escape: Capsule Dynamics, AMR, and Vaccine Design in zoonotic Streptococcus suis

Project outline

Streptococcus suis is a swine pathogen and emerging zoonotic agent causing severe human infections like meningitis and septicaemia. Endemic in pigs, management is challenged by genetic diversity, rising antimicrobial resistance (AMR), and its primary virulence factor: the capsular polysaccharide (CPS).

CPS defines S. suis serotypes, dictating host adaptation and virulence. Current vaccines are serotype-specific, making CPS diversity crucial for control. Short-read sequencing fails to resolve repetitive CPS locus structures, obscuring evolution. Crucially, ""capsule switching"" via horizontal gene transfer allows strains to evade host immunity and vaccines, mirroring Streptococcus pneumoniae.

This project uses global data, in addition to long-read sequencing to decode S. suis capsule evolution. Combining genomics, structural biology, and epidemiology, we examine how capsule switching interacts with AMR and virulence to inform vaccine design and predict escape.

  • Objective 1: Reconstruction of the entire capsule locus: Using global human/pig WGS data, the student will apply Oxford Nanopore long-read sequencing to build complete assemblies of repetitive CPS loci, establishing a blueprint of capsular diversity.
  • Objective 2: Mapping phenotypic correlates via protein networks: Grouping capsule proteins into structural similarity networks will cluster serotypes by molecular homology rather than serology alone. Aligning networks with phenotypic data will identify domains linked to virulence, host specificity, and cross-reactivity for vaccine targets.
  • Objective 3: Modelling capsule switching, pathogenicity, and AMR co-selection: Using phylogenetic models and molecular clock analysis, the student will reconstruct capsule switching trajectories, modelling co-selection with AMR genes and virulence factors to assess vaccine escape risks.

Principal Supervisor

Dr Lucy Weinert

Email address: lw461@cam.ac.uk

Department / Partner Institute: Veterinary Medicine

Website: https://www.vet.cam.ac.uk/staff/dr-lucy-weinert

BBSRC strategic theme

Bioscience for sustainable agriculture and food