Research projects within proteases and chaperones – how they orchestra pathogenesis of Staphylococcus aureus

Virulence gene regulation

Staphylococcus aureus produces a wide range of toxins that is uses to cause disease. Examples are the enterotoxins that cause food-poisoning, and TST-1 that causes the fatal disease toxic shock syndrome. Inactivation of the ClpXP protease abolished expression of most toxin genes and rendered S. aureus avirulent. ClpXP thus represents a promising target of antimicrobials, and a major aim of our research is to gain insight into the molecular mechanisms that link the ClpP protease to virulence gene regulation.

Coordination of cell wall synthesis and cell division

Cell division is required for growth of all bacterial populations and bacterial cell division proteins have attracted increasing interest as targets for antibiotics. The processes of cell division and septum formation need to be tightly co-ordinated in order to avoid cell lysis and we are currently investigating how the ClpX chaperone and the ClpXP protease contribute to these processes.

Last line defences against antibiotic resistant Staphylococcus aureus

The aim of the project is to elucidate how the chaperone ClpX contributes to development of resistance to the last line anti-staphylococcal agent daptomycin. Specifically, we will address if daptomycin resistance and immune escape mechanisms coevolve, thus increasing the likelihood of treatment failure.

Factors contributing  to high level resistance towards cell-wall targeting antibiotics

Clinical MRSA isolates exhibit very different resistance levels and, interestingly, the variation in resistance levels does not correlate with expression of the resistance gene, mecA (encoding PBP2a), clearly demonstrating that intrinsic factors contribute to the resistance levels, and we are currently investigating some of these factors.

Extracellular vesicles as vehicles for toxins

The aim of this project is to use genetic approaches to investigate the molecular principles that govern membrane vesicle formation in S. aureus, and state-of-the-art quantitative proteomics to investigate the protein content of vesicles