Dr Toska Wonfor

• PhD in Microbiology, University of Bath (2023)
• MBiolSci in Molecular Biology, University of Sheffield (2019)

Toska is currently undertaking her first postdoctoral research position, having joined the Geoghegan group at the University of Birmingham in January 2023. Her work is conducted in collaboration with the Wellcome Sanger Institute as part of the CARRIAGE Project, which leverages genome-wide association studies (GWAS) to compare the genomes and microbiomes of Staphylococcus aureus carriers and non-carriers. The goal is to gain a deeper understanding of the mechanisms driving S. aureus colonisation. Toska’s role involves experimentally validating host-pathogen interactions identified through GWAS to elucidate the specific roles of the associated genes in colonisation processes.

Before her position here in Birmingham, Toska completed her PhD at the University of Bath, where she studied S. aureus evasion of the complement system.

Staphylococcus aureus is an opportunistic pathogen responsible for diseases ranging from mild skin infections to severe sepsis. Its significant health burden underscores the need to understand its infection and colonisation mechanisms to develop effective therapeutics.

Understanding the factors involved in S. aureus colonisation.

Staphylococcus aureus asymptomatically colonises approximately 30% of the population, however, carriage significantly increases the risk of subsequent infection, making decolonisation a promising strategy for infection prevention. Colonisation is influenced by bacterial determinants, host factors and the microbiome, all of which contribute to host susceptibility and require deeper understanding to inform strategies that intercept these mechanisms.

To identify bacterial determinants, one approach is to examine adaptive mutations that enable S. aureus to thrive during colonisation.  Our recent genome-wide association study found mutations in the cell-wall anchored protein SraP as significantly associated with colonisation. Initially linked with attachment to damaged heart valves during endocarditis, SraP was later found to bind sialic acid, a sugar abundant on nasal epithelial cells, suggesting a role in mediating attachment during colonisation. Our research aims to uncover how the mutations in SraP alter its function to facilitate colonisation.

To investigate host factors, the CARRIAGE genome-wide association study is currently analysing the genomes of over 20,000 UK participants to identify differences between persistently colonised and non-colonised individuals. Our work will validate these findings to elucidate how specific host genes enable or inhibit colonisation.

Staphylococcus aureus evasion of the complement system.

Staphylococcus aureus employs a diverse array of virulence factors to evade and neutralise the host immune system. A key element of the host’s innate defence is the complement system, a proteolytic cascade of plasma proteins that recruits immune effectors to infection sites, labels pathogens for efficient phagocytosis and assembles into a pore-forming complex to directly lyse cells. Among pathogens, S. aureus has an unusually large repertoire of complement disarming proteins, collectively termed complement evasins (CEs).

During her PhD at the University of Bath, Toska developed novel assays to investigate which CE factors are most important in disabling the complement system, and the diversity of this defence system among clinical isolates, with the objective of developing therapeutics to interfere with these proteins and increase pathogen susceptibility to the innate immune system.