Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification
Streptococcus pneumoniae evades C3-mediated opsonization and effector functions by expressing an immuno-protective polysaccharide capsule and Factor H (FH)-binding proteins. Here we use super-resolution microscopy, mutants and functional analysis to show how these two defense mechanisms are function...
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sg-ntu-dr.10356-891232020-11-01T05:12:50Z Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification Pathak, Anuj Bergstrand, Jan Sender, Vicky Spelmink, Laura Aschtgen, Marie-Stephanie Muschiol, Sandra Widengren, Jerker Henriques-Normark, Birgitta Lee Kong Chian School of Medicine (LKCMedicine) Singapore Centre for Environmental Life Sciences and Engineering C3b Deposition DRNTU::Science::Medicine Binding Proteins Streptococcus pneumoniae evades C3-mediated opsonization and effector functions by expressing an immuno-protective polysaccharide capsule and Factor H (FH)-binding proteins. Here we use super-resolution microscopy, mutants and functional analysis to show how these two defense mechanisms are functionally and spatially coordinated on the bacterial cell surface. We show that the pneumococcal capsule is less abundant at the cell wall septum, providing C3/C3b entry to underlying nucleophilic targets. Evasion of C3b deposition at division septa and lateral amplification underneath the capsule requires localization of the FH-binding protein PspC at division sites. Most pneumococcal strains have one PspC protein, but successful lineages in colonization and disease may have two, PspC1 and PspC2, that we show affect virulence differently. We find that spatial localization of these FH-recruiting proteins relative to division septa and capsular layer is instrumental for pneumococci to resist complement-mediated opsonophagocytosis, formation of membrane-attack complexes, and for the function as adhesins. Published version 2018-09-24T06:02:18Z 2019-12-06T17:18:23Z 2018-09-24T06:02:18Z 2019-12-06T17:18:23Z 2018 Journal Article Pathak, A., Bergstrand, J., Sender, V., Spelmink, L., Aschtgen, M.-S., Muschiol, S., . . . Henriques-Normark, B. (2018). Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification. Nature Communications, 9(1), 3398-. doi:10.1038/s41467-018-05494-w https://hdl.handle.net/10356/89123 http://hdl.handle.net/10220/46073 10.1038/s41467-018-05494-w en Nature Communications © 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. 16 p. application/pdf |
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C3b Deposition DRNTU::Science::Medicine Binding Proteins Pathak, Anuj Bergstrand, Jan Sender, Vicky Spelmink, Laura Aschtgen, Marie-Stephanie Muschiol, Sandra Widengren, Jerker Henriques-Normark, Birgitta Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification |
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Streptococcus pneumoniae evades C3-mediated opsonization and effector functions by expressing an immuno-protective polysaccharide capsule and Factor H (FH)-binding proteins. Here we use super-resolution microscopy, mutants and functional analysis to show how these two defense mechanisms are functionally and spatially coordinated on the bacterial cell surface. We show that the pneumococcal capsule is less abundant at the cell wall septum, providing C3/C3b entry to underlying nucleophilic targets. Evasion of C3b deposition at division septa and lateral amplification underneath the capsule requires localization of the FH-binding protein PspC at division sites. Most pneumococcal strains have one PspC protein, but successful lineages in colonization and disease may have two, PspC1 and PspC2, that we show affect virulence differently. We find that spatial localization of these FH-recruiting proteins relative to division septa and capsular layer is instrumental for pneumococci to resist complement-mediated opsonophagocytosis, formation of membrane-attack complexes, and for the function as adhesins. |
author2 |
Lee Kong Chian School of Medicine (LKCMedicine) |
author_facet |
Lee Kong Chian School of Medicine (LKCMedicine) Pathak, Anuj Bergstrand, Jan Sender, Vicky Spelmink, Laura Aschtgen, Marie-Stephanie Muschiol, Sandra Widengren, Jerker Henriques-Normark, Birgitta |
format |
Article |
author |
Pathak, Anuj Bergstrand, Jan Sender, Vicky Spelmink, Laura Aschtgen, Marie-Stephanie Muschiol, Sandra Widengren, Jerker Henriques-Normark, Birgitta |
author_sort |
Pathak, Anuj |
title |
Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification |
title_short |
Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification |
title_full |
Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification |
title_fullStr |
Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification |
title_full_unstemmed |
Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification |
title_sort |
factor h binding proteins protect division septa on encapsulated streptococcus pneumoniae against complement c3b deposition and amplification |
publishDate |
2018 |
url |
https://hdl.handle.net/10356/89123 http://hdl.handle.net/10220/46073 |
_version_ |
1683493157089574912 |