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Uncovering pathogenic mechanisms in methicillin resistant Staphylococcus aureus

Primary Supervisor: Professor Joan Geoghegan, Institute of Microbiology and Infection

Secondary supervisor: Professor Willem van Schaik, University of Birmingham, Professor Julie Morrissey, University of Leicester.

PhD project title: Uncovering pathogenic mechanisms in methicillin resistant Staphylococcus aureus.

University of Registration: University of Birmingham

Project outline:

Methicillin resistant Staphylococcus aureus (MRSA) causes infections in humans that are extremely challenging to treat. MRSA possesses a vast repertoire of cell wall-anchored proteins (CWAPs) that mediate interactions with the host and underpin its versatility as a pathogen. CWAPs promote bacterial adhesion, invasion of host cells, immune evasion and biofilm formation. For example, CWAP interactions with fibrinogen and fibrin allow the bacteria to aggregate with fibrin networks or to recruit soluble fibrinogen to the bacterial surface during infection (Pickering et al., 2019). Interaction with the corneocyte protein corneodesmosin facilitates adhesion of S. aureus to the surface of the skin (Towell et al., 2021). Research in Dr Geoghegan’s lab focuses on understanding the contribution of CWAPs to MRSA infection at the molecular level. The aim of this project is to advance our knowledge of the MRSA-host interaction and pathogenesis by investigating how CWAPs are influenced by the host environment during infection. This cutting-edge research project will focus on understanding the effects of the nasal microbiota, pathogenic bacteria, and host factors, such as proteases, on CWAP activity.

Key objectives will be to:

  1. Establish how the activity of CWAPs is modulated in complex environments that mimic those at infection sites and how this influences the microbe-host interaction.
  2. Understand how host- and bacterium-derived proteases alter CWAP activity.
  3. Investigate the influence of the microbiota and bacterial pathogens that colonise the nasal passage on the virulence of MRSA.

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 with the University of Leicester. The student will be trained in a range of molecular microbiology techniques, transcriptome profiling, proteomics, recombinant protein production and mammalian cell culture.

References:

  1. Towell et al., (2021). Staphylococcus aureus binds to the N-terminal region of corneodesmosin to adhere to the stratum corneum in atopic dermatitis. Proc Natl Acad Sci USA. 118(1):e2014444118.
  2. Pickering et al. (2019). Host-specialized fibrinogen-binding by a bacterial surface protein promotes biofilm formation and innate immune evasion. PLoS Pathogens. 15(6):e1007816.

BBSRC Strategic Research Priority: Understanding the Rules of Life: Microbiology

Techniques that will be undertaken during the project:

Molecular microbiology techniques, transcriptome profiling using next generation sequencing, proteomics, recombinant protein production and cutting-edge cell culture models.

Contact:Professor Joan Geoghegan, University of Birmingham