A new pathway of staphylococcal pathogenesis: apoptosis-like death induced by Staphopain B in human neutrophils and monocytes.
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.
Smagur
Jan
J
Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, Poland.
Guzik
Krzysztof
K
Magiera
Lukasz
L
Bzowska
Malgorzata
M
Gruca
Milosz
M
Thøgersen
Ida B
IB
Enghild
Jan J
JJ
Potempa
Jan
J
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
D017305:Annexin A1; D039481:CD11b Antigen; D003546:Cysteine Endopeptidases; C479137:staphopain B protein, Staphylococcus aureus