TY  - JOUR
U1  - Zeitschriftenartikel, wissenschaftlich - begutachtet (reviewed)
A1  - Surmann, Kristin
A1  - Michalik, Stephan
A1  - Hildebrandt, Petra
A1  - Gierok, Philipp
A1  - Depke, Maren
A1  - Brinkmann, Lars
A1  - Bernhardt, Jörg
A1  - Salazar, Manuela G.
A1  - Sun, Zhi
A1  - Shteynberg, David
A1  - Kusebauch, Ulrike
A1  - Moritz, Robert L.
A1  - Wollscheid, Bernd
A1  - Lalk, Michael
A1  - Völker, Uwe
A1  - Schmidt, Frank
T1  - Comparative proteome analysis reveals conserved and specific adaptation patterns of Staphylococcus aureus after internalization by different types of human non-professional phagocytic host cells
N2  - Staphylococcus aureus is a human pathogen that can cause a wide range of diseases. Although formerly regarded as extracellular pathogen, it has been shown that S. aureus can also be internalized by host cells and persist within these cells. In the present study, we comparatively analyzed survival and physiological adaptation of S. aureus HG001 after internalization by two human lung epithelial cell lines (S9 and A549), and human embryonic kidney cells (HEK 293). Combining enrichment of bacteria from host-pathogen assays by cell sorting and quantitation of the pathogen's proteome by mass spectrometry we characterized S. aureus adaptation during the initial phase between 2.5 h and 6.5 h post-infection. Starting with about 2 × 106 bacteria, roughly 1450 S. aureus proteins, including virulence factors and metabolic enzymes were identified by spectral comparison and classical database searches. Most of the bacterial adaptation reactions, such as decreased levels of ribosomal proteins and metabolic enzymes or increased amounts of proteins involved in arginine and lysine biosynthesis, enzymes coding for terminal oxidases and stress responsive proteins or activation of the sigma factor SigB were observed after internalization into any of the three cell lines studied. However, differences were noted in central carbon metabolism including regulation of fermentation and threonine degradation. Since these differences coincided with different intracellular growth behavior, complementary profiling of the metabolome of the different non-infected host cell types was performed. This revealed similar levels of intracellular glucose but host cell specific differences in the amounts of amino acids such as glycine, threonine or glutamate. With this comparative study we provide an impression of the common and specific features of the adaptation of S. aureus HG001 to specific host cell environments as a starting point for follow-up studies with different strain isolates and regulatory mutants.
KW  - -
KW  - human cell lines
KW  - host-pathogen interaction
KW  - proteomics
KW  - label-free quantitation
UN  - https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-29533
SN  - 1664-302X
SS  - 1664-302X
U6  - https://doi.org/10.3389/fmicb.2014.00392
DO  - https://doi.org/10.3389/fmicb.2014.00392
VL  - 5
PB  - Frontiers Media S.A.
ER  -