In this project we have characterized in detail the mode of division and the morphological changes that occur during the cell cycle of the important pathogen Staphylococcus aureus. We have corrected statements present in the literature for the last five decades by demonstrating that, contrary to what was previously thought, S. aureus cells (i) do not necessarily divide in three orthogonal planes over three consecutive division cycle and (ii) are capable of slight cell elongation, which may be important for invading certain infection niches.
We have also uncovered new, surprising, levels of regulation during cell cycle progression. The best example links a cytoplasmic protein involved in chromosome segregation, FtsK, and a protein anchored at the outer layer of the cell (the cell wall), required for splitting of the division septum, Sle1. We found that FtsK regulates the levels of Sle1 so that the cell can delay septum splitting while chromosome segregation is taking place, or when DNA damage occurs. Tight regulation of the timing of septum splitting during the cell cycle is essential to avoid exposure of an immature cell surface, which would be easily recognized by the infected host, leading to clearance of the bacterial cells by the innate immune system.
A second example of progress beyond the state of the art was the imaging of single molecules of peptidoglycan synthases in live, dividing S. aureus cells, and the demonstration that their processive movement is driven by the enzymatic activity of the proteins (and not by the cytoskeleton, as previously proposed) and therefore can be stopped with cell wall-targeting antibiotics, such as beta-lactams or vancomycin.
Overall, this project allowed significant progress in our understanding of the cell cycle of an important bacterial pathogen, as well as the development of useful tools for the study and screening of antibiotics.
