title: A new pathway of staphylococcal pathogenesis: apoptosis-like death induced by Staphopain B in human neutrophils and monocytes.
abstract: Circulating neutrophils and monocytes form the first line of cellular defense against invading bacteria. Here, we describe a novel and specific mechanism of disabling and eliminating phagocytes by Staphylococcus aureus. Staphopain B (SspB) selectively cleaved CD11b on phagocytes, which rapidly acquired features of cell death. SspB-treated phagocytes expressed phosphatidylserine as well as annexin I and became permeable to propidium iodide, thus demonstrating distinctive features of both apoptosis and necrosis, respectively. The cell death observed was caspase and Syk tyrosine kinase independent, whilst cytochalasin D efficiently inhibited the staphopain-induced neutrophil killing. Neutrophil and monocyte cell death was not affected by integrin clustering ligands (ICAM-1 or fibrin) and was prevented, and even reversed, by IgG. This protective effect was dependent on the Fc fragment, collectively suggesting cooperation of the CD16 receptor and integrin Mac-1 (CD11b/CD18). We conclude that SspB, particularly in the presence of staphylococcal protein A, may reduce the number of functional phagocytes at infection sites, thus facilitating colonization and dissemination of S. aureus.
authors.affiliation: Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Smagur
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Guzik
authors.forename: Lukasz
authors.initials: L
authors.lastname: Magiera
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Bzowska
authors.forename: Milosz
authors.initials: M
authors.lastname: Gruca
authors.forename: Ida B
authors.initials: IB
authors.lastname: Thøgersen
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Enghild
authors.forename: Jan
authors.initials: J
authors.lastname: Potempa
mesh_terms: D017305:Annexin A1 / Q000378:metabolism; D017209:Apoptosis; D039481:CD11b Antigen / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D013203:Staphylococcal Infections / Q000276:immunology* / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000254:growth & development
chemical_list: D017305:Annexin A1; D039481:CD11b Antigen; D003546:Cysteine Endopeptidases; C479137:staphopain B protein, Staphylococcus aureus