MiCoCo

A proteomics approach to understand physiology and virulence of Staphylococcus aureus

Prof. Dr. Susanne Engelmann

Microbial Proteomics, Helmholtz Centre for Infection Research, Braunschweig

Staphylococcus aureus is a human pathogen of strong clinical significance due to increasing infections with multi-resistant isolates. A better understanding of its infection biology is urgently required to combat this pathogen also in the future. The fitness of this pathogen, which is based on its ability to successfully adapt to host conditions, is crucial for full virulence. During colonization and infection, S. aureus is confronted with a multitude of signals including growth-limiting factors and life-threatening host defense mechanisms. Therefore, adaptation of bacterial gene expression in their natural habitat is a multi-signal response and it will be a challenging task for future studies to unravel this diverse network. We established an S. aureus protein expression database Aureolib containing 4,692 time dependent expression profiles for 521 cytoplasmic proteins under nine infection relevant, well defined laboratory conditions. Initially, this data base was used as a tool box to get new insights into S. aureus adaptation to more complex, infection-relevant experimental models such as nasal secretions, milk and macrophages. For that purpose we used a green fluorescence protein (GFP) expressing S. aureus Newman strain and analyzed its expression of intracellular and surface associated proteins under these conditions by mass spectrometry in combination with isotopic protein labeling. We found evidence that under these conditions S. aureus copes with various nutrient limitations (e. g. carbon and iron sources).  Moreover, we found that proteins necessary for tissue adhesion and immune evasion are preferentially expressed in cells grown in nasal secretions and macrophages whereas toxins and exoenzymes are repressed at the same time.