دورية أكاديمية
Complement evasion factor (CEF), a novel immune evasion factor of Streptococcus pyogenes
| العنوان: | Complement evasion factor (CEF), a novel immune evasion factor of Streptococcus pyogenes |
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| المؤلفون: | Haniyeh Aghababa, Yi Tian Ting, Devaki Pilapitiya, Jacelyn M.S. Loh, Paul G. Young, Thomas Proft |
| المصدر: | Virulence, Vol 13, Iss 1, Pp 225-240 (2022) |
| بيانات النشر: | Taylor & Francis Group, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Infectious and parasitic diseases |
| مصطلحات موضوعية: | streptococcus pyogenes, group a streptococcus, immune evasion, complement, complement deposition, galleria mellonella infection model, glycan-binding, Infectious and parasitic diseases, RC109-216 |
| الوصف: | Streptococcus pyogenes, a leading human pathogen, is responsible for a wide range of diseases, including skin and soft tissue infections and severe invasive diseases. S. pyogenes produces a large arsenal of virulence factors, including several immune evasion factors. We have identified an open reading frame (spy0136) in the S. pyogenes 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 S. pyogenes. We therefore named the previously unknown protein ‘complement evasion factor’ (CEF). An S. pyogenes Δspy0136/cef deletion mutant showed decreased virulence in an in-vitro whole blood killing assay and a Galleria mellonella (wax moth) infection model. Furthermore, an L. lactis spy0136/cef gain-of-function mutant showed increased survival during growth in whole human blood. Analysis of serum samples from patients with invasive S. pyogenes revealed Spy0136/CEF sero-conversion indicating expression during disease. In summary, we have identified a novel S. pyogenes immune evasion factor that binds to several complement proteins to interfere with complement function. This is the first example of a S. pyogenes virulence factor binding to several different target proteins via glycan-dependent interactions. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2150-5594 2150-5608 21505594 |
| العلاقة: | https://doaj.org/toc/2150-5594Test; https://doaj.org/toc/2150-5608Test |
| DOI: | 10.1080/21505594.2022.2027629 |
| الوصول الحر: | https://doaj.org/article/9ba5dab223574f529bcd0c7819a75fbfTest |
| رقم الانضمام: | edsdoj.9ba5dab223574f529bcd0c7819a75fbf |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 21505594 21505608 |
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| DOI: | 10.1080/21505594.2022.2027629 |