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dc.contributor.authorFOSTER, TIMOTHY JAMESen
dc.date.accessioned2010-04-27T13:54:53Z
dc.date.available2010-04-27T13:54:53Z
dc.date.issued2008en
dc.date.submitted2008en
dc.identifier.citationKubica, M., Guzik, K., Koziel, J., Zarebski, M., Richter, W., Gajkowska, B., Golda, A., Maciag-Gudowska, A., Brix, K., Shaw, L., Foster, T.J., Potempa, J. , A potential new pathway for Staphylococcus aureus dissemination: silent survival of S.aureus phagocytosed by human monocyte-derived macrophages., PloS One, 3, 2008, e1409-en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/39214
dc.descriptionPUBLISHEDen
dc.description.abstractAlthough considered to be an extracellular pathogen, Staphylococcus aureus is able to invade a variety of mammalian, non-professional phagocytes and can also survive engulfment by professional phagocytes such as neutrophils and monocytes. In both of these cell types S. aureus promptly escapes from the endosomes/phagosomes and proliferates within the cytoplasm, which quickly leads to host cell death. In this report we show that S. aureus interacted with human monocyte-derived macrophages in a very different way to those of other mammalian cells. Upon phagocytosis by macrophages, S. aureus persisted intracellularly in vacuoles for 3-4 days before escaping into the cytoplasm and causing host cell lysis. Until the point of host cell lysis the infected macrophages showed no signs of apoptosis or necrosis and were functional. They were able to eliminate intracellular staphylococci if prestimulated with interferon-gamma at concentrations equivalent to human therapeutic doses. S. aureus survival was dependent on the alternative sigma factor B as well as the global regulator agr, but not SarA. Furthermore, isogenic mutants deficient in alpha-toxin, the metalloprotease aureolysin, protein A, and sortase A were efficiently killed by macrophages upon phagocytosis, although with different kinetics. In particular alpha-toxin was a key effector molecule that was essential for S. aureus intracellular survival in macrophages. Together, our data indicate that the ability of S. aureus to survive phagocytosis by macrophages is determined by multiple virulence factors in a way that differs considerably from its interactions with other cell types. S. aureus persists inside macrophages for several days without affecting the viability of these mobile cells which may serve as vehicles for the dissemination of infection.en
dc.description.sponsorshipThis work was supported by the Commission of the European Communities, specific RTD program "Quality of Life and Management of Living Resources", Project QLRT-2001-01250 "Novel non-antibiotic treatment of staphylococcal diseases", grants from the State Committee for Scientific Research (MNiSW, Warsaw, Poland) (KBN 6PO4A 060 19; 2P04A 049 28; 2PO4A 011 26 , 6PO4A 011 27 to KG, JK, MZ and MK respectively) and the European Molecular Biology Organization for a research fellowship (ASTF 103-05) awarded to MK. JP is a recipient of a Subsydium Profesorskie awarded by the Foundation for Polish Science (FNP, Warsaw, Poland). TJF would like to acknowledge support from Science Foundation Ireland, the Health Research Board and The Wellcome Trust.en
dc.format.extente1409en
dc.language.isoenen
dc.relation.ispartofseriesPloS Oneen
dc.relation.ispartofseries3en
dc.rightsYen
dc.subjectMicrobiology
dc.titleA potential new pathway for Staphylococcus aureus dissemination: silent survival of S.aureus phagocytosed by human monocyte-derived macrophages.en
dc.contributor.sponsorHealth Research Board
dc.contributor.sponsorWellcome Trust
dc.contributor.sponsorScience Foundation Ireland
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/tfosteren
dc.identifier.rssinternalid49151en


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