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Understanding how interaction with the host influences virulence and antimicrobial resistance in Staphylococcus aureus

Principal Supervisor: Professor Joan Geoghegan 

Secondary Supervisor(s): Dr Tim Overton

University of Registration: University of Birmingham

BBSRC Research Themes: Understanding the Rules of Life (Microbiology)

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Deadline: 4 January, 2024


Project Outline

Adhesion is a fundamental step during bacterial colonisation and infection of a host. Staphylococcus aureus possesses a vast repertoire of cell wall-anchored proteins that facilitate adhesion to host molecules and surfaces. Research in the staphylococcal pathogenesis lab focuses on understanding the factors that contribute to the success of Staphylococcus aureus as a commensal and pathogen and using this information to discover new targets for decolonisation or treatment of infection. The aim of this project is to advance our understanding of the bacterium-host interaction by discovering how adhesion alters key phenotypic traits in S. aureus. By combining a variety of different experimental approaches, this project will investigate how sensing a host surface and interacting with it impacts on virulence and susceptibility to antibiotics and host defences in bacterial populations.

Key objectives will be to:

  1. Establish how the expression and activity of cell wall-anchored proteins is modulated by the sensing of and adhesion to a substrate in S. aureus.
  2. Discover how the production and activity of S. aureus virulence factors is influenced by the sensing of host molecules and surfaces.
  3. Discover how susceptibility to antimicrobial agents and host defences changes following interactions with host molecules.

The student will join a collegiate interdisciplinary research group within the Institute of Microbiology and Infection (IMI) at University of Birmingham and benefit from an established collaboration between Professor Joan Geoghegan and Dr Tim Overtons’ groups. The student will be trained in a range of molecular microbiology and infection biology techniques, single cell analysis, transcriptional profiling and proteomics

References

  • Da Costa TM et al., (2022). Fibronectin binding protein B binds to loricrin and promotes corneocyte adhesion by Staphylococcus aureus. Nature Communications. 13: 2517.
  • Geoghegan JA & DufrĂȘne YF (2018). Mechanomicrobiology: How Mechanical Forces Activate Staphylococcus aureus Adhesion. Trends Microbiol. (8):645-648.
  • Geoghegan JA & Foster TJ (2017) Cell Wall-Anchored Surface Proteins of Staphylococcus aureus: Many Proteins, Multiple Functions. Curr Top Microbiol Immunol. 409:95-120.

Techniques

Molecular microbiology techniques, single cell analysis, transcriptional profiling using next generation sequencing, advanced microscopy, flow cytometry, proteomics, cell culture