title: Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain.
abstract: Host cell invasion is a major feature of Staphylococcus aureus and contributes to infection development. The intracellular metabolically active bacteria can induce host cell activation and death but they can also persist for long time periods. In this study a comparative analysis was performed of different well-characterized S. aureus strains in their interaction with a variety of host cell types. Staphylococcus aureus (strains 6850, USA300, LS1, SH1000, Cowan1) invasion was compared in different human cell types (epithelial and endothelial cells, keratinocytes, fibroblasts, osteoblasts). The number of intracellular bacteria was determined, cell inflammation was investigated, as well as cell death and phagosomal escape of bacteria. To explain strain-dependent differences in the secretome, a proteomic approach was used. Barrier cells took up high amounts of bacteria and were killed by aggressive strains. These strains expressed high levels of toxins, and possessed the ability to escape from phagolysosomes. Osteoblasts and keratinocytes ingested less bacteria, and were not killed, even though the primary osteoblasts were strongly activated by S. aureus. In all cell types S. aureus was able to persist. Strong differences in uptake, cytotoxicity, and inflammatory response were observed between primary cells and their corresponding cell lines, demonstrating that cell lines reflect only partially the functions and physiology of primary cells. This study provides a contribution for a better understanding of the pathomechanisms of S. aureus infections. The proteomic data provide important basic knowledge on strains commonly used in the analysis of S. aureus-host cell interaction.
authors.affiliation: University Hospital of Muenster, Institute of Medical Microbiology, Muenster, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Strobel
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Pförtner
authors.affiliation: Institute of Medical Microbiology, Jena University Hospital, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Tuchscherr
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Völker
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: Westfaelische-Wilhelms University, Institute of Anatomy and Vascular Biology, Muenster, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Kramko
authors.affiliation: Westfaelische-Wilhelms University, Institute of Anatomy and Vascular Biology, Muenster, Germany.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Schnittler
authors.affiliation: Department of Microbiology, Biocenter, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: M J
authors.initials: MJ
authors.lastname: Fraunholz
authors.affiliation: Institute of Medical Microbiology, Jena University Hospital, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Löffler
authors.affiliation: University Hospital of Muenster, Institute of Medical Microbiology, Muenster, Germany; Cluster of Excellence EXC 1003, Cells in Motion, Muenster, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Peters
authors.affiliation: University Hospital of Muenster, Institute of Medical Microbiology, Muenster, Germany. Electronic address: silke.niemann@uni-muenster.de.
authors.forename: S
authors.initials: S
authors.lastname: Niemann
mesh_terms: D016923:Cell Death; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D054884:Host-Pathogen Interactions; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D009928:Organ Specificity; D010588:Phagosomes / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D013203:Staphylococcal Infections / Q000378:metabolism / Q000382:microbiology; D013211:Staphylococcus aureus / Q000502:physiology*
chemical_list: D016207:Cytokines
keywords: Cytotoxicity; Host cell invasion; Inflammatory response; Persistence; Proteomics; Staphylococcus aureus