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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)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
289
issue
47
publisher
ASBMB
external identifiers
  • pmid:25281746
  • wos:000345335000010
  • scopus:84911909640
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
2014-11-05 20:23:18
date last changed
2017-10-22 03:07:27
@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    = {ASBMB},
  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},
  volume       = {289},
  year         = {2014},
}