Project Reference: TRG27-VET-MM1

Project title: Genomic Signatures of Host Adaptation and Spillover in Staphylococcus aureus

Project outline

Staphylococcus aureus is a major cause of disease in humans and animals and an important reservoir of antimicrobial resistance (AMR). Some lineages are adapted to a single host, while others are host generalists. Host jumps can introduce new resistance and virulence determinants, yet we do not understand what enables a lineage to cross a species barrier and successfully adapt to a new host.

For the first time, the scale of available genomic data makes it possible to investigate host adaptation across S. aureus at the species level, rather than focusing on individual lineages or outbreaks. This project will combine this global perspective with clonal complex- and lineage-specific analyses to determine whether mechanisms of host adaptation are shared across the species or are lineage-specific.

More than 140,000 publicly available genomes will be examined, and those with host, geographic and temporal information will be used to map host association across the global population. Phylogenetic analyses will identify host specialists and generalists, reconstruct independent host jumps and compare their evolutionary trajectories.

Comparative genomics will identify AMR determinants, virulence factors and mobile genetic elements (MGEs) associated with particular hosts or host groups. By analysing repeated host transitions across the species and within individual lineages, we will distinguish convergent signatures of host adaptation from lineage-specific evolutionary changes while accounting for shared ancestry.

We will trace the movement and host range of MGEs and investigate whether different hosts leave characteristic mutational signatures in bacterial genomes. Integrating species-wide and lineage-specific analyses will reveal whether host adaptation follows predictable evolutionary routes, identify hidden reservoirs and transmission pathways, and test whether genomic signatures can predict which lineages have the greatest potential to cross species boundaries.

Principal Supervisor

Dr Marta Matuszewska

Email address: mm2211@cam.ac.uk

Department / Partner Institute: Veterinary Medicine

Website: https://www.infectiousdisease.cam.ac.uk/directory/marta-matuszewska

BBSRC strategic theme

Understanding the rules of life