Current research themes
Cell wall Structure
The cell wall of bacteria is vital for cell growth and viability. The major component of the cell wall is the large polymer peptidoglycan, which provides strength to the wall, as well as being the scaffold for the other cell wall polymers such as teichoic acids and surface proteins. The synthesis of peptidoglycan is the target of some of our most commonly used antibiotics, so understanding this dynamic structure may help elucidate new potential drug targets for the treatment of MRSA infections. Our research aims to refine our understanding of the importance of cell wall structure in pathogenesis and cell growth.
Augmentation of S. aureus infection
by commensal bacteria
by commensal bacteria
Augmentation is the phenomenon where the pathogenicity of S. aureus is increased, or "augmented", by the presence of human skin commensals or derivative materials such as peptidoglycan. We are investigating how the presence of these commensals leads to increased infection establishment and dissemination.
Our recent paper on the augmentation project:
Human skin commensals augment Staphylococcus aureus pathogenesis (Boldock, 2018)
Super Resolution Localisation of Surface Proteins
Recent work done by our lab has shown, through Atomic Force Microscopy, that the cell wall of S. aureus has a more complex architecture than previously thought (Pasquina Lemonche, 2020). Mature cell wall peptidoglycan appears as a porous, mesh-like structure, while newly formed cell wall material forms a concentric ring structure.
Continuing on from this fantastic work, we want to know: where are the surface proteins within this architecture?
S. aureus has over thirty surface proteins that contribute towards disease progression. By using super resolution microscopy and genetic engineering, we're working towards answering that question.
Maintenance of S. aureus viability
The bacterial envelope is essential for viability, with peptidoglycan being the major stress-bearing cell wall polymer that can withstand the high internal cellular turgor pressure in Staphylococcus aureus. The exoplasmic space, between the cell membrane and the cell wall, is of greatest importance, as it is where the final stages of peptidoglycan synthesis occur and where many antibiotics like penicillin act. There is still a lot to elucidate about the maintenance and role of the exoplasm in bacterial viability. To achieve this, we pair up molecular approaches with microscopy techniques like transmission electron microscopy (TEM). TEM allows us to study the structural differences between various mutants and treatments by imaging ultrathin-sections of S. aureus. TEM is an excellent technique that provides detail into the cell envelope, bacterial integrity and its maintenance.
Life and Death
Although antibiotics have been used for many decades, and the mechanistic of the action of antibiotics is well studied, the events chain that leads to cell death is still unkown. By taking a more synoptic approach, using the major human pathogen Staphylococcus aureus, to elucidate cell wall dynamic processes that are essential for growth (life) and the bactericidal effects of antibiotics (death) leading to a simple set of underlying principles requiring both coordinated peptidoglycan synthesis and hydrolysis of peptidoglycan. Many techniques are used to perform this research, such as super-resolution fluorescence microscopy, TEM, Atomic Force Microscopy and pathogenisis, all working in a coordinated manner.