Factor H binding proteins protect division septa on encapsulated Streptococcus pneumoniae against complement C3b deposition and amplification

Nature Communications
Anuj PathakBirgitta Henriques-Normark

Abstract

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.

References

Jan 1, 1984·Annual Review of Immunology·K A JoinerM M Frank
Mar 1, 1981·Reviews of Infectious Diseases·A Tomasz
Sep 1, 2000·The Journal of Biological Chemistry·R JanulczykL Bjorck
Apr 9, 2001·Infection and Immunity·S DaveL S McDaniel
Aug 14, 2003·Molecular Immunology·Hanna JarvaSeppo Meri
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandhya DaveLarry S McDaniel
Dec 13, 2005·Analytical Biochemistry·Robert KarlssonDavid G Myszka
Apr 7, 2006·The Journal of Biological Chemistry·Ling LuJing-Ren Zhang
Jun 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guillermo MadicoSanjay Ram
Aug 25, 2006·Nature·Fredric CarlssonGunnar Lindahl
Oct 3, 2006·Biophysical Journal·Jonathan W D ComeauPaul W Wiseman
Feb 13, 2008·FEMS Microbiology Reviews·André ZapunMariana G Pinho
Jun 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Teresia HallströmKristian Riesbeck
Mar 22, 2012·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Dalia DenapaiteWaldemar Vollmer
Jul 16, 2013·Environmental Microbiology·Orietta MassiddaWaldemar Vollmer
Jul 23, 2013·Cellular Microbiology·Evelien T M BerendsSuzan H M Rooijakkers
Sep 7, 2013·The Journal of Infectious Diseases·Sarah BrowallBirgitta Henriques-Normark
Nov 6, 2013·Proceedings of the National Academy of Sciences of the United States of America·Kumaravel KandaswamyKimberly A Kline
Nov 26, 2013·Biochimica Et Biophysica Acta·Olaf Schneewind, Dominique Missiakas
Dec 4, 2014·Nature·Aurore FleurieChristophe Grangeasse
May 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Thomas R Larson, Janet Yother

❮ Previous
Next ❯

Citations

Jul 14, 2020·Indian Journal of Microbiology·Shikhar SharmaDeepak Gaur
Oct 6, 2020·Frontiers in Immunology·Alexander TilleMarc Thilo Figge
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Vicky SenderBirgitta Henriques-Normark
Oct 20, 2020·American Journal of Respiratory and Critical Care Medicine·Federico Iovino, Birgitta Henriques-Normark
Mar 22, 2020·Molecular Immunology·Deepak KumarSherry D Fleming
Mar 16, 2021·Frontiers in Immunology·Sara R MooreViviana P Ferreira
Aug 12, 2021·Trends in Molecular Medicine·Bharathi SundareshTim van Opijnen
Nov 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Rei NakamotoLok-To Sham

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
fluorescence microscopy
peptide exchange
PCR
electrophoresis
size exclusion chromatography
peptide array
fluorescence
surface plasmon resonance
chip

Software Mentioned

Imspector
MATLAB
Genescript
GraphPad Prism

Related Concepts

Related Feeds

Bacterial Pneumonia (ASM)

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Antibody-Dependent Cell Cytotoxicity

Antibody-dependent cellular toxicity refers to the lysis of a target cell by a non-sensitized effector cell of the immune system as a result of antibodies binding to the target cell membrane and engaging the Fc receptors on the immune effector cells. Find the latest research on antibody-dependent cellular toxicity here.

Alternative Complement Pathway

The Alternative Complement Pathway is part of the innate immune system, and activation generates membrane attack complexes that kill pathogenic cells. Discover the latest research on the Alternative Complement Pathway.

Bacterial Pneumonia

Bacterial pneumonia is a prevalent and costly infection that is a significant cause of morbidity and mortality in patients of all ages. Here is the latest research.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.