Understanding S. aureus as an intracellular bacterial pathogen
Duration: 40 weeks
Detalhes
BACKGROUND
In Europe, the burden caused by antibiotic resistant bacterial infections is equivalent to influenza, HIV/Aids and Tuberculosis combined. Infections caused by Staphylococcus aureus (S. aureus) strains are the second most relevant in this context. A chief factor suggested to contribute for the high incidence and prevalence of S. aureus infections is its capacity to persist and divide inside host cells, escaping antibiotics and extracellular immune recognition. Formerly regarded as an exclusively extracellular pathogen, S. aureus is in fact a facultative intracellular pathogen. S. aureus can infect immune and non-immune cells and evade autonomous immunity (intracellular recognition of pathogens). This is thought to be a major factor in continuance of carriage, chronicity of infection and dissemination within the host. In an extracellular context the resolving power and live-cell compatibility of super-resolution microscopy has allowed to perform a comprehensive characterization of S. aureus cell division progression (10.1038/ncomms9055). Based on morphology changes (e.g. septum formation at mid-cell), S. aureus cell division can be divided into 3 different phases: phase 1-cells prior to division septum initiation, phase 2-cells undergoing septum synthesis, phase 3-division septum is complete prior to splitting into to two daughter cells. Importantly, these phases are altered as a consequence of different challenges (e.g. antibiotics). Further, it also permitted to understand the subcellular localization and antibiotic induced changes to a multitude of important S. aureus cell division proteins (10.1038/nature25506).
OBJECTIVES
A wealth of knowledge that needs to be expanded to an infection context in order to truly understand the cell biology of this bacterial pathogen as well as the role of antibiotics in the context of infection. Here we aim to take advantage of this comprehensive characterization as the basis to explore S. aureus cell division inside host cells. We will infect human cells with S. aureus strains and characterize the morphology changes associated with S. aureus cell division progression (TASK 1) as well as the subcellular localization of key cell division proteins (TASK 2). Finally, we will explore the effect antimicrobial molecules have on these processes and organization (TASK 3). This master project will provide training in microbiology, cell biology and microscopy.