## 1 Introduction  
The Gram positive bacterium _Staphylococcus aureus_ is not only a permanent commensal of about 20% of the world population but also an opportunistic pathogen [1; 2]. Infections can result in diverse clinical manifestations such as soft local tissue infections, endocarditis, sepsis and also pneumonia [2; 3]. _S. aureus_ has been described earlier as an extracellular pathogen that exhibits its pathogenicity with the secretion of virulence factors [4]. Within the last two decades, however, _S. aureus_ has also been recognized as an invasive pathogen with an intracellular lifestyle [5; 6]. It was shown by proteomic and transcriptomic studies that intracellular _S. aureus_ undergoes changes in expression of metabolic genes, nutrient transporters and virulence factors to adapt to the intracellular environment [7; 8].  
To prevent colonization in the human lung, the respiratory epithelium maintains an effective antimicrobial environment. This is accomplished by various antimicrobial strategies such as forming a physical barrier, mucociliary clearance, and production of antimicrobial peptides, surfactant proteins,complement, chemokines, and cytokines [9; 10; 11]. Many of these defence mechanisms are activated by staphylococcal virulence factors [12] but so far only little is known about the consequences on the host cell metabolism. Recently, we described the effect of staphylococcal alpha toxin (Hla) on glycolysis and glutaminolysis of human airway epithelial cells [13]. Although this study shows that the host metabolism is affected by the action of single virulence factors, the complex process of infection might influence the host cell metabolism very differently. During the invasion process _S. aureus_ adherence proteins such as fibronectin binding proteins bind to host cell structures such as \(\alpha_{5}\beta_{1}\) integrin via fibronectin and induce a zipper-type uptake [14]. The uptake activates the rearrangement of the cytoskeleton [15] and several regulators that are also involved in metabolism such as the PI3K-Akt pathway [16; 17; 18]. Moreover, cellular processes that are directly coupled to the host metabolism such as autophagy [19] and apoptosis [20] are affected by _S. aureus_. In between this complex interplay of cellular processes and signalling events metabolites serve as signal molecules, precursors for antimicrobial effector molecules and also fuel primary anabolic and catabolic pathways. From the view of the intracellular pathogen the host cell metabolome represents a source of nutrients [21]. Interestingly, only adapted bacteria are able to grow in this environment [22]. Therefore, alterations in the host cell metabolite composition also affect the intracellular pathogen.  
In this work the host cell metabolome of A549 human airway epithelial cells was examined and the effect of the infection with _S. aureus_ was elucidated on the intracellular and extracellular level. We observed in infected A549 cells a strongly reduced uptake of nutrients, especially of essential amino acids. Moreover the analysis of the intracellular metabolic profiles in a time dependent manner showed dynamic changes in the content of free amino acids and certain nucleotides. Furthermore, we elucidated that the de novo synthesis of purine and pyrimidine nucleotides is shut down after infection by using metabolic inhibitors and a metabolic labelling approach.