title: Staphylococcus aureus induces caspase-independent cell death in human peritoneal mesothelial cells.
abstract: Bacterial peritonitis remains a serious complication of peritoneal dialysis. Although Staphylococcus epidermidis is the most common pathogen involved, infections with Staphylococcus aureus lead to severe peritoneal damage and are often associated with a dramatic loss of mesothelial cells. Induction of cell death appears to be involved in peritoneal damage and mesothelial cell loss during bacterial infections. Using cultured human peritoneal mesothelial cells (HMCs), we investigated the ability of different S. epidermidis and S. aureus strains to damage the HMC monolayer and to trigger cell death. We show that only a subgroup of live S. aureus isolates, characterized by an invasive and alpha-hemolysin-producing phenotype, induces cell death. None of the tested S. epidermidis strains, which were not invasive or hemolytic, had a cytotoxic effect. After host cell invasion, S. aureus resided within phagocytic vacuoles, and HMCs were apparently able to degrade staphylococci. However, even after prolonged infection, a high percentage of S. aureus remained alive within HMCs and might be released after host cell death. Cell death induced by S. aureus was accompanied by apoptotic alterations, such as DNA fragmentation, but was independent of endogenous FasL and tumor necrosis factor-alpha death ligand expression. Moreover, caspases were not involved in S. aureus-induced mesothelial cell death. In conclusion, our data indicate that mesothelial cell death might represent a major mechanism of S. aureus-induced damage of the peritoneum during bacterial peritonitis.
authors.affiliation: Institute of Medical Microbiology, University Hospital of Münster, Münster, Germany. bettina.loeffler@web.de
authors.forename: B
authors.initials: B
authors.lastname: Haslinger-Löffler
authors.forename: B
authors.initials: B
authors.lastname: Wagner
authors.forename: M
authors.initials: M
authors.lastname: Brück
authors.forename: K
authors.initials: K
authors.lastname: Strangfeld
authors.forename: M
authors.initials: M
authors.lastname: Grundmeier
authors.forename: U
authors.initials: U
authors.lastname: Fischer
authors.forename: W
authors.initials: W
authors.lastname: Völker
authors.forename: G
authors.initials: G
authors.lastname: Peters
authors.forename: K
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: B
authors.initials: B
authors.lastname: Sinha
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D018929:Cell Culture Techniques; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008954:Models, Biological; D009852:Omentum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010538:Peritonitis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D010588:Phagosomes / Q000382:microbiology / Q000648:ultrastructure; D013211:Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048069:Tumor Necrosis Factors / Q000494:pharmacology
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D020169:Caspases