Project Reference: TRG27-VET-LW2

Project title: Bats as bacterial zoonotic threats – evolution and mechanisms of bat-adapted Staphylococcus aureus

Project outline

Staphylococcus aureus is a WHO high-priority pathogen causing diseases from skin infections to sepsis. This project investigates the recent discovery that S. aureus is widespread in bat populations and exhibits genomic signatures of bat adaptation. While bat-borne viruses are widely studied, bats as reservoirs for bacterial pathogens remain underexplored.

Preliminary work reveals bat S. aureus sequence types are shared with human and livestock isolates, indicating recent interspecies transmission, with persistent carriage detected in bat handlers. Yet, bat isolates phylogenetically cluster and harbour a novel plasmid encoding two undescribed proteins, including an uncharacterized MSCRAMM (Microbial Surface Components Recognizing Adhesive Matrix Molecules) – likely involved in bat host adaptation.

S. aureus persistence in bats presents a spillover threat to humans. This interdisciplinary project addresses this across three scales:

  • Objective 1: Evolutionary trajectories (with Dr. Lucy Weinert): Analyse international whole-genome sequencing data to map bat, human, and livestock S. aureus phylogenies. Apply molecular clock models to trace emergence, track plasmid epidemiology and horizontal gene transfer, and identify AMR or virulence genes.
  • Objective 2: Structural characterization of MSCRAMM (with Prof. Joan Geoghegan): Elucidate how the plasmid MSCRAMM drives host adherence. Use AlphaFold3 modeling, express and purify the protein, and screen extracellular matrix libraries to identify host targets and measure binding kinetics.
  • Objective 3: Pathogenicity and colonisation dynamics (with Prof. Clare Bryant): Evaluate the capacity of bat-adapted S. aureus to breach host barriers. Using human and bat cell lines, assess adherence, internalization, intracellular survival, and host innate immune responses.

References:

Matuszewska et al. (2022): PMID 35762208

Foster et al. (2014): 24336184

Fountain et al. (2022): 35931727

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 an integrated understanding of health