A proteomic perspective of the interplay of Staphylococcus aureus and human alveolar epithelial cells during infection

Surmann, Kristin; Simon, Marjolaine; Hildebrandt, Petra; Pförtner, Henrike; Michalik, Stephan; Stentzel, Sebastian; Steil, Leif; Dhople, Vishnu M.; Bernhardt, Jörg; Schlüter, Rabea; Depke, Maren; Gierok, Philipp; Lalk, Michael; Bröker, Barbara M.; Schmidt, Frank; Völker, Uwe

doi:10.1016/j.jprot.2015.07.034

Cited by 23 publications

(30 citation statements)

References 62 publications

(82 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proteasomal activity by the immunoproteasome upon infection stress can be induced by the cytokine IFN-γ [45]. Moreover, IFN-γ is released in response to S. aureus and immunoproteasomal mRNAs were found expressed in infected A549 cells [46]. Therefore the combination of an early alpha-toxin activity and a late host-response might lead to time dependent changes in the intracellular amino acid profile.…”

Section: Discussionmentioning

confidence: 99%

“…RSH contains an amino acid sensing domain, whereas the latter two enzymes lack this domain and are most likely involved in the response to cell wall stress [52]. Recently, it was shown, that RSH is downregulated in intracellular S. aureus cells but the other two (p)ppGpp synthetases are upregulated [46]. This is in line with our finding that the amount of amino acids is increasing in the host cytosol, whereas cell wall stress due to phagosomal activity is likely to occur.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Staphylococcus aureus Infection Reduces Nutrition Uptake and Nucleotide Biosynthesis in a Human Airway Epithelial Cell Line

et al. 2016

Self Cite

View full text Add to dashboard Cite

Abstract:The Gram positive opportunistic human pathogen Staphylococcus aureus induces a variety of diseases including pneumonia. S. aureus is 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 ( 1 H-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 after S. aureus infection. 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 with S. aureus negatively affects growth, alters the metabolic composition and specifically impacts the de novo nucleotide biosynthesis in this human airway epithelial cell model.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus Infection Reduces Nutrition Uptake and Nucleotide Biosynthesis in a Human Airway Epithelial Cell Line

et al. 2016

Self Cite

View full text Add to dashboard Cite

show abstract

“…Using a FACS-based enrichment protocol for quantitative proteome profiling of internalized S. aureus in human airway epithelial cells [119], almost 1500 S. aureus proteins were identified with highly sensitive MS equipment from only 2 × 10 6 bacterial cells [139]. Furthermore, we recently developed a workflow for the simultaneous assessment of both the bacterial and the host cell proteomes (using SILAC quantification), showing that intra-cellular persisting bacteria were growing slowly, induced the stringent response, and had to cope with microaerobic conditions as well as with cell wall stress [144]. A pilot proteomics study on murine S. aureus pneumonia demonstrates that proteomics are feasible for ex vivo samples, such as bronchoalveolar lavages [145].…”

Section: Omics Technologies In S Aureus Researchmentioning

confidence: 99%

“…Finally, antibody binding is a good lead for T-cell antigen selection, since the development of high affinity antibodies requires T-cell help in most cases [152]. For targeting S. aureus persisting inside host cells comprehensive information about the transcription profile of the bacteria as well as the proteome produced by them is invaluable [95,139,144]. …”

Section: Omics Technologies In S Aureus Vaccine Developmentmentioning

confidence: 99%

Omics Approaches for the Study of Adaptive Immunity to Staphylococcus aureus and the Selection of Vaccine Candidates

et al. 2016

Self Cite

View full text Add to dashboard Cite

Staphylococcus aureus is a dangerous pathogen both in hospitals and in the community. Due to the crisis of antibiotic resistance, there is an urgent need for new strategies to combat S. aureus infections, such as vaccination. Increasing our knowledge about the mechanisms of protection will be key for the successful prevention or treatment of S. aureus invasion. Omics technologies generate a comprehensive picture of the physiological and pathophysiological processes within cells, tissues, organs, organisms and even populations. This review provides an overview of the contribution of genomics, transcriptomics, proteomics, metabolomics and immunoproteomics to the current understanding of S. aureus‑host interaction, with a focus on the adaptive immune response to the microorganism. While antibody responses during colonization and infection have been analyzed in detail using immunoproteomics, the full potential of omics technologies has not been tapped yet in terms of T-cells. Omics technologies promise to speed up vaccine development by enabling reverse vaccinology approaches. In consequence, omics technologies are powerful tools for deepening our understanding of the “superbug” S. aureus and for improving its control.

show abstract

“…Such techniques are regularly applied for host cells interacting with bacterial pathogens [152,153]. In contrast, flow cytometry cell sorting techniques of filamentous fungi are not generally advisable due to the cell size and the morphologic heterogeneity of hyphal cells.…”

Section: Challenges In the Simultaneous Dual Proteome Analysis Of mentioning

confidence: 99%

Challenges and Strategies for Proteome Analysis of the Interaction of Human Pathogenic Fungi with Host Immune Cells

et al. 2015

View full text Add to dashboard Cite

Opportunistic human pathogenic fungi including the saprotrophic mold Aspergillus fumigatus and the human commensal Candida albicans can cause severe fungal infections in immunocompromised or critically ill patients. The first line of defense against opportunistic fungal pathogens is the innate immune system. Phagocytes such as macrophages, neutrophils and dendritic cells are an important pillar of the innate immune response and have evolved versatile defense strategies against microbial pathogens. On the other hand, human-pathogenic fungi have sophisticated virulence strategies to counteract the innate immune defense. In this context, proteomic approaches can provide deeper insights into the molecular mechanisms of the interaction of host immune cells with fungal pathogens. This is crucial for the identification of both diagnostic biomarkers for fungal infections and therapeutic targets. Studying host-fungal interactions at the protein level is a challenging endeavor, yet there are few studies that have been undertaken. This review draws attention to proteomic techniques and their application to fungal pathogens and to challenges, difficulties, and limitations that may arise in the course of simultaneous dual proteome analysis of host immune cells interacting with diverse morphotypes of fungal pathogens. On this basis, we discuss strategies to overcome these multifaceted experimental and analytical challenges including the viability of immune cells during co-cultivation, the increased and heterogeneous protein complexity of the host proteome dynamically interacting with the fungal proteome, and the demands on normalization strategies in terms of relative quantitative proteome analysis.

show abstract

A proteomic perspective of the interplay of Staphylococcus aureus and human alveolar epithelial cells during infection

Cited by 23 publications

References 62 publications

Staphylococcus aureus Infection Reduces Nutrition Uptake and Nucleotide Biosynthesis in a Human Airway Epithelial Cell Line

Staphylococcus aureus Infection Reduces Nutrition Uptake and Nucleotide Biosynthesis in a Human Airway Epithelial Cell Line

Omics Approaches for the Study of Adaptive Immunity to Staphylococcus aureus and the Selection of Vaccine Candidates

Challenges and Strategies for Proteome Analysis of the Interaction of Human Pathogenic Fungi with Host Immune Cells

Contact Info

Product

Resources

About