Full functional activity of SSL7 requires binding of both complement C5 and IgA

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dc.contributor.author Lorenz, Natalie en
dc.contributor.author Clow, F en
dc.contributor.author Radcliff, Fiona en
dc.contributor.author Fraser, John en
dc.date.accessioned 2018-10-26T02:30:54Z en
dc.date.issued 2013-08 en
dc.identifier.issn 0818-9641 en
dc.identifier.uri http://hdl.handle.net/2292/43523 en
dc.description.abstract Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a range of diseases, from local skin infections through to life-threatening illnesses such as toxic shock syndrome. S. aureus produces an assortment of molecules designed to evade or subvert the host immune system. One example is the 23 kDa staphylococcal superantigen-like protein 7 (SSL7) that simultaneously binds immunoglobulin A (IgA) and complement C5 to inhibit complement-mediated hemolytic and bactericidal activity. The avirulent bacterium Lactococcus lactis was engineered to express SSL7 so that its role in bacterial survival could be assessed without interference from other virulence factors. Expression of SSL7 by L. lactis led to significantly enhanced bacterial survival in whole human blood and prevented the membrane attack complex (C5b-9) forming on the cell wall. To further understand the mechanism of action of SSL7, the activity of wild-type SSL7 protein was compared with a panel of mutant proteins lacking the capacity to bind IgA, C5, or both IgA and C5. SSL7 potently inhibited in vitro chemotaxis of inflammatory myeloid cells in response to a pathogenic stimulus and when injected into mice, SSL7 blocked the migration of neutrophils into the peritoneum in response to an inoculum of heat-killed S. aureus. Mutagenesis of the C5-binding site on SSL7 abolished all inhibitory activity, while mutation of the IgA-binding site had only partial effects, indicating that while IgA binding enhances activity it is not essential. SSL7 is an important staphylococcal virulence factor with potent anti-inflammatory properties, which are mediated by targeting complement C5 and IgA. en
dc.publisher Nature Publishing Group: Open Access Hybrid Model Option B en
dc.relation.ispartofseries Immunology and Cell Biology en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm en
dc.title Full functional activity of SSL7 requires binding of both complement C5 and IgA en
dc.type Journal Article en
dc.identifier.doi 10.1038/icb.2013.28 en
pubs.begin-page 469 en
pubs.volume 91 en
dc.rights.holder Copyright: The author en
dc.identifier.pmid 23797068 en
pubs.author-url http://www.nature.com/icb/journal/v91/n7/full/icb201328a.html en
pubs.end-page 476 en
dc.rights.accessrights http://purl.org/eprint/accessRights/RestrictedAccess en
pubs.subtype Article en
pubs.elements-id 396839 en
pubs.org-id Medical and Health Sciences en
pubs.org-id Medical Sciences en
pubs.org-id Molecular Medicine en
pubs.org-id Science en
pubs.org-id Science Research en
pubs.org-id Maurice Wilkins Centre (2010-2014) en
dc.identifier.eissn 1440-1711 en
pubs.record-created-at-source-date 2013-11-18 en
pubs.dimensions-id 23797068 en


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