Staphylococcus aureus Infection Reduces Nutrition Uptake and Nucleotide Biosynthesis in a Human Airway Epithelial Cell Line.
The Gram positive opportunistic human pathogenStaphylococcus aureusinduces a variety of diseases including pneumonia.S. aureusis the second most isolated pathogen in cystic fibrosis patients and accounts for a large proportion of nosocomial pneumonia. Inside the lung, the human airway epithelium is the first line in defence with regard to microbial recognition and clearance as well as regulation of the immune response. The metabolic host response is, however, yet unknown. To address the question of whether the infection alters the metabolome and metabolic activity of airway epithelial cells, we used a metabolomics approach. The nutrition uptake by the human airway epithelial cell line A549 was monitored over time by proton magnetic resonance spectroscopy (¹H-NMR) and the intracellular metabolic fingerprints were investigated by gas chromatography and high performance liquid chromatography (GC-MS) and (HPLC-MS). To test the metabolic activity of the host cells, glutamine analogues and labelled precursors were applied after the infection. We found that A549 cells restrict uptake of essential nutrients from the medium afterS. aureusinfection. Moreover, the infection led to a shutdown of the purine and pyrimidine synthesis in the A549 host cell, whereas other metabolic routes such as the hexosamine biosynthesis pathway remained active. In summary, our data show that the infection withS. aureusnegatively affects growth, alters the metabolic composition and specifically impacts the de novo nucleotide biosynthesis in this human airway epithelial cell model.
Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany. gierokp47@uni-greifswald.de.
Philipp
P
Gierok
Competence Center Functional Genomics, Junior Research Group Pathoproteomics, University of Greifswald, 17487 Greifswald, Germany. manuela.harms@uni-greifswald.de.
Manuela
M
Harms
Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany. methling@uni-greifswald.de.
Karen
K
Methling
Competence Center Functional Genomics, Junior Research Group Pathoproteomics, University of Greifswald, 17487 Greifswald, Germany. falko.hochgraefe@uni-greifswald.de.
Falko
F
Hochgräfe
Institute of Biochemistry, University of Greifswald, 17487 Greifswald, Germany. lalk@uni-greifswald.de.
Michael
M
Lalk
Staphylococcus aureus; host cell metabolism; infection; metabolomics