Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/94782
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dc.contributor.authorHarvey, R.en
dc.contributor.authorHughes, C.en
dc.contributor.authorPaton, A.en
dc.contributor.authorTrappetti, C.en
dc.contributor.authorPaton, J.en
dc.contributor.authorTweten, R.en
dc.date.issued2014en
dc.identifier.citationPLoS One, 2014; 9(8):e103625-1-e103625-9en
dc.identifier.issn1932-6203en
dc.identifier.issn1932-6203en
dc.identifier.urihttp://hdl.handle.net/2440/94782-
dc.description.abstractStreptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306). However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467) to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2), p19 subunit of IL-23 (IL23A) and IFNβ (IFNB1) compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism.en
dc.description.statementofresponsibilityMansour Ebrahimi, Parisa Aghagolzadeh, Narges Shamabadi, Ahmad Tahmasebi, Mohammed Alsharifi, David L. Adelson, Farhid Hemmatzadeh, Esmaeil Ebrahimieen
dc.language.isoengen
dc.publisherPLOSen
dc.rights© 2014 Harvey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectCells, Cultured; Macrophages; Animals; Mice; Streptococcus pneumoniae; Bacterial Proteins; Granulocyte-Macrophage Colony-Stimulating Factor; DNA Primers; Streptolysins; Blotting, Western; Enzyme-Linked Immunosorbent Assay; Analysis of Variance; Polymerase Chain Reaction; Sequence Analysis, DNA; Species Specificity; Interleukin-1beta; Inflammasomesen
dc.titleThe impact of pneumolysin on the macrophage response to Streptococcus pneumoniae is strain-dependenten
dc.typeJournal articleen
dc.identifier.rmid0030008794en
dc.identifier.doi10.1371/journal.pone.0103625en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/565526en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/627142en
dc.identifier.pubid85228-
pubs.library.collectionMolecular and Biomedical Science publicationsen
pubs.library.teamDS01en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidTrappetti, C. [0000-0001-8272-0068]en
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]en
Appears in Collections:Molecular and Biomedical Science publications

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