dc.contributor.author |
Aghababa, Haniyeh |
|
dc.contributor.author |
Ting, Yi Tian |
|
dc.contributor.author |
Pilapitiya, Devaki |
|
dc.contributor.author |
Loh, Jacelyn MS |
|
dc.contributor.author |
Young, Paul G |
|
dc.contributor.author |
Proft, Thomas |
|
dc.coverage.spatial |
United States |
|
dc.date.accessioned |
2022-05-17T02:02:51Z |
|
dc.date.available |
2022-05-17T02:02:51Z |
|
dc.date.issued |
2022-12 |
|
dc.identifier.citation |
Virulence 13(1):225-240 Dec 2022 |
|
dc.identifier.issn |
2150-5594 |
|
dc.identifier.uri |
https://hdl.handle.net/2292/59277 |
|
dc.description.abstract |
<i>Streptococcus pyogenes</i>, a leading human pathogen, is responsible for a wide range of diseases, including skin and soft tissue infections and severe invasive diseases. <i>S. pyogenes</i> produces a large arsenal of virulence factors, including several immune evasion factors. We have identified an open reading frame (<i>spy0136</i>) in the <i>S. pyogenes</i> SF370 genome encoding a protein of unknown function. Using recombinant Spy0136 in a pull-down assay with human plasma and ELISA, we have identified four complement proteins (C1r, C1s, C3, and C5) as binding partners. Treatment of the complement proteins with PNGase F abrogated binding to C1s, C3, and C5, indicating glycan-dependent interactions. rSpy0136 inhibited complement-mediated hemolysis and interfered with all three complement pathways in a Wieslab complement assay. Furthermore, rSpy0136 inhibited deposition of the C3b opsonin and the membrane attack complex (MAC) on the surface of <i>S. pyogenes</i>. We therefore named the previously unknown protein 'complement evasion factor' (CEF).An <i>S. pyogenes Δspy0136/cef</i> deletion mutant showed decreased virulence in an <i>in-vitro</i> whole blood killing assay and a <i>Galleria mellonella</i> (wax moth) infection model. Furthermore, an <i>L. lactis spy0136/cef</i> gain-of-function mutant showed increased survival during growth in whole human blood. Analysis of serum samples from patients with invasive <i>S. pyogenes</i> revealed Spy0136/CEF sero-conversion indicating expression during disease. In summary, we have identified a novel <i>S. pyogenes</i> immune evasion factor that binds to several complement proteins to interfere with complement function. This is the first example of a <i>S. pyogenes</i> virulence factor binding to several different target proteins via glycan-dependent interactions. |
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dc.format.medium |
Print |
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dc.language |
eng |
|
dc.publisher |
Informa UK Limited |
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dc.relation.ispartofseries |
Virulence |
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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. |
|
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
|
dc.rights.uri |
https://creativecommons.org/licenses/by/4.0/ |
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dc.subject |
Galleria mellonella infection model |
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dc.subject |
Group A Streptococcus |
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dc.subject |
Streptococcus pyogenes |
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dc.subject |
complement |
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dc.subject |
complement deposition |
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dc.subject |
glycan-binding |
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dc.subject |
immune evasion |
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dc.subject |
Clinical Research |
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dc.subject |
Infectious Diseases |
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dc.subject |
Foodborne Illness |
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dc.subject |
Prevention |
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dc.subject |
Emerging Infectious Diseases |
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dc.subject |
2.1 Biological and endogenous factors |
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dc.subject |
1.1 Normal biological development and functioning |
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dc.subject |
Infection |
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dc.subject |
Science & Technology |
|
dc.subject |
Life Sciences & Biomedicine |
|
dc.subject |
Immunology |
|
dc.subject |
Infectious Diseases |
|
dc.subject |
Microbiology |
|
dc.subject |
Streptococcus pyogenes |
|
dc.subject |
Group A Streptococcus |
|
dc.subject |
immune evasion |
|
dc.subject |
complement |
|
dc.subject |
complement deposition |
|
dc.subject |
Galleria mellonella infection model |
|
dc.subject |
glycan-binding |
|
dc.subject |
GROUP-A STREPTOCOCCUS |
|
dc.subject |
PROTEIN |
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dc.subject |
BINDING |
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dc.subject |
C5 |
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dc.subject |
TRANSCRIPTOME |
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dc.subject |
LOCALIZATION |
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dc.subject |
DEGRADATION |
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dc.subject |
INHIBITION |
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dc.subject |
EXPRESSION |
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dc.subject |
PEPTIDASE |
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dc.subject |
0501 Ecological Applications |
|
dc.subject |
0605 Microbiology |
|
dc.subject |
1108 Medical Microbiology |
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dc.title |
Complement evasion factor (CEF), a novel immune evasion factor of <i>Streptococcus pyogenes</i>. |
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dc.type |
Journal Article |
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dc.identifier.doi |
10.1080/21505594.2022.2027629 |
|
pubs.issue |
1 |
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pubs.begin-page |
225 |
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pubs.volume |
13 |
|
dc.date.updated |
2022-04-04T01:02:22Z |
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dc.rights.holder |
Copyright: The author |
en |
pubs.author-url |
https://www.ncbi.nlm.nih.gov/pubmed/35094646 |
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pubs.end-page |
240 |
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pubs.publication-status |
Accepted |
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dc.rights.accessrights |
http://purl.org/eprint/accessRights/OpenAccess |
en |
pubs.subtype |
research-article |
|
pubs.subtype |
Journal Article |
|
pubs.elements-id |
881469 |
|
dc.identifier.eissn |
2150-5608 |
|
pubs.online-publication-date |
2022-1-30 |
|