Streptococcus pneumoniae phosphoglycerate kinase is a novel complement inhibitor affecting the membrane attack complex formation.
Blom, Anna LU
; Bergmann, Simone
; Fulde, Marcus
; Riesbeck, Kristian
LU
and Agarwal, Vaibhav
LU
(2014)
In Journal of Biological Chemistry
289(47).
- Abstract
- The Gram-positive bacterium Streptococcus pneumoniae is a major human pathogen that causes infections ranging from acute otitis media to life-threatening invasive disease. Pneumococci have evolved several strategies to circumvent the host immune response, in particular the complement attack. The pneumococcal glycolytic enzyme phosphoglycerate kinase (PGK) is both secreted and bound to the bacterial surface and simultaneously binds plasminogen and its activator tPA. In the present study, we demonstrate that PGK has an additional role in modulating the complement attack. PGK interacted with the membrane attack complex (MAC) components C5, C7 and C9, thereby blocking the assembly and membrane insertion of MAC resulting in significant... (More)
- The Gram-positive bacterium Streptococcus pneumoniae is a major human pathogen that causes infections ranging from acute otitis media to life-threatening invasive disease. Pneumococci have evolved several strategies to circumvent the host immune response, in particular the complement attack. The pneumococcal glycolytic enzyme phosphoglycerate kinase (PGK) is both secreted and bound to the bacterial surface and simultaneously binds plasminogen and its activator tPA. In the present study, we demonstrate that PGK has an additional role in modulating the complement attack. PGK interacted with the membrane attack complex (MAC) components C5, C7 and C9, thereby blocking the assembly and membrane insertion of MAC resulting in significant inhibition of the hemolytic activity of human serum. Recombinant PGK interacted in a dose-dependent manner with these terminal pathway proteins, and the interactions were ionic in nature. In addition, PGK inhibited C9 polymerization both in the fluid phase and on the surface of sheep erythrocytes. Interestingly, PGK bound several MAC proteins simultaneously. While C5 and C7 had partially overlapping binding sites on PGK, C9 did not compete with either one for PGK binding. Moreover, PGK significantly inhibited MAC deposition via both the classical and alternative pathway at the pneumococcal surface. Additionally, upon activation plasmin(ogen) bound to PGK cleaved the central complement protein C3b thereby further modifying the complement attack. In conclusion, our data demonstrate for the first time, to our knowledge, a novel pneumococcal inhibitor of the terminal complement cascade aiding complement evasion by this important pathogen. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4738181
- author
- Blom, Anna
LU
; Bergmann, Simone
; Fulde, Marcus
; Riesbeck, Kristian
LU
and Agarwal, Vaibhav
LU
- organization
- publishing date
- 2014
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 289
- issue
- 47
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:25281746
- wos:000345335000010
- scopus:84911909640
- pmid:25281746
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M114.610212
- language
- English
- LU publication?
- yes
- id
- 7a504027-4d4c-4bd8-8e6b-cd8a091bc4e1 (old id 4738181)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/25281746?dopt=Abstract
- date added to LUP
- 2016-04-01 10:06:23
- date last changed
- 2022-02-02 06:28:30
@article{7a504027-4d4c-4bd8-8e6b-cd8a091bc4e1,
abstract = {{The Gram-positive bacterium Streptococcus pneumoniae is a major human pathogen that causes infections ranging from acute otitis media to life-threatening invasive disease. Pneumococci have evolved several strategies to circumvent the host immune response, in particular the complement attack. The pneumococcal glycolytic enzyme phosphoglycerate kinase (PGK) is both secreted and bound to the bacterial surface and simultaneously binds plasminogen and its activator tPA. In the present study, we demonstrate that PGK has an additional role in modulating the complement attack. PGK interacted with the membrane attack complex (MAC) components C5, C7 and C9, thereby blocking the assembly and membrane insertion of MAC resulting in significant inhibition of the hemolytic activity of human serum. Recombinant PGK interacted in a dose-dependent manner with these terminal pathway proteins, and the interactions were ionic in nature. In addition, PGK inhibited C9 polymerization both in the fluid phase and on the surface of sheep erythrocytes. Interestingly, PGK bound several MAC proteins simultaneously. While C5 and C7 had partially overlapping binding sites on PGK, C9 did not compete with either one for PGK binding. Moreover, PGK significantly inhibited MAC deposition via both the classical and alternative pathway at the pneumococcal surface. Additionally, upon activation plasmin(ogen) bound to PGK cleaved the central complement protein C3b thereby further modifying the complement attack. In conclusion, our data demonstrate for the first time, to our knowledge, a novel pneumococcal inhibitor of the terminal complement cascade aiding complement evasion by this important pathogen.}},
author = {{Blom, Anna and Bergmann, Simone and Fulde, Marcus and Riesbeck, Kristian and Agarwal, Vaibhav}},
issn = {{1083-351X}},
language = {{eng}},
number = {{47}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Streptococcus pneumoniae phosphoglycerate kinase is a novel complement inhibitor affecting the membrane attack complex formation.}},
url = {{http://dx.doi.org/10.1074/jbc.M114.610212}},
doi = {{10.1074/jbc.M114.610212}},
volume = {{289}},
year = {{2014}},
}