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Haemophilus influenzae protein E recognizes the C-terminal domain of vitronectin and modulates the membrane attack complex.

Singh, Birendra LU ; Jalalvand, Farshid LU ; Mörgelin, Matthias LU ; Zipfel, Peter; Blom, Anna LU and Riesbeck, Kristian LU (2011) In Molecular Microbiology 81. p.80-98
Abstract
Haemophilus influenzae protein E (PE) is a 16 kDa adhesin that induces a pro-inflammatory immune response in lung epithelial cells. The active epithelial binding region comprising amino acids PE 84-108 also interferes with complement-mediated bacterial killing by capturing vitronectin (Vn) that prevents complement deposition and formation of the membrane attack complex (MAC). Here, the interaction between PE and Vn was characterized using site-directed mutagenesis. Protein E variants were produced both in soluble forms and in surface-expressed molecules on Escherichia coli. Mutations within PE(84-108) in the full-length molecule revealed that K85 and R86 residues were important for the Vn binding. Bactericidal activity against H.... (More)
Haemophilus influenzae protein E (PE) is a 16 kDa adhesin that induces a pro-inflammatory immune response in lung epithelial cells. The active epithelial binding region comprising amino acids PE 84-108 also interferes with complement-mediated bacterial killing by capturing vitronectin (Vn) that prevents complement deposition and formation of the membrane attack complex (MAC). Here, the interaction between PE and Vn was characterized using site-directed mutagenesis. Protein E variants were produced both in soluble forms and in surface-expressed molecules on Escherichia coli. Mutations within PE(84-108) in the full-length molecule revealed that K85 and R86 residues were important for the Vn binding. Bactericidal activity against H. influenzae was higher in human serum pre-treated with full-length PE as compared with serum incubated with PE(K85E, R86D) , suggesting that PE quenched Vn. A series of truncated Vn molecules revealed that the C-terminal domain comprising Vn(353-363) harboured the major binding region for PE. Interestingly, MAC deposition was significantly higher on mutants devoid of PE due to a decreased Vn-binding capacity when compared with wild-type H. influenzae. Our results define a fine-tuned interaction between H. influenzae and the innate immune system, and identify the mode of control of the MAC that is important for pathogen complement evasion. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Microbiology
volume
81
pages
80 - 98
publisher
Wiley-Blackwell
external identifiers
  • wos:000292106200007
  • pmid:21542857
  • scopus:79959572234
ISSN
1365-2958
DOI
10.1111/j.1365-2958.2011.07678.x
language
English
LU publication?
yes
id
dd4b5446-600e-40c9-b7bd-dc5b91c4b59a (old id 1973173)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21542857?dopt=Abstract
date added to LUP
2011-06-07 13:55:25
date last changed
2017-08-27 05:47:05
@article{dd4b5446-600e-40c9-b7bd-dc5b91c4b59a,
  abstract     = {Haemophilus influenzae protein E (PE) is a 16 kDa adhesin that induces a pro-inflammatory immune response in lung epithelial cells. The active epithelial binding region comprising amino acids PE 84-108 also interferes with complement-mediated bacterial killing by capturing vitronectin (Vn) that prevents complement deposition and formation of the membrane attack complex (MAC). Here, the interaction between PE and Vn was characterized using site-directed mutagenesis. Protein E variants were produced both in soluble forms and in surface-expressed molecules on Escherichia coli. Mutations within PE(84-108) in the full-length molecule revealed that K85 and R86 residues were important for the Vn binding. Bactericidal activity against H. influenzae was higher in human serum pre-treated with full-length PE as compared with serum incubated with PE(K85E, R86D) , suggesting that PE quenched Vn. A series of truncated Vn molecules revealed that the C-terminal domain comprising Vn(353-363) harboured the major binding region for PE. Interestingly, MAC deposition was significantly higher on mutants devoid of PE due to a decreased Vn-binding capacity when compared with wild-type H. influenzae. Our results define a fine-tuned interaction between H. influenzae and the innate immune system, and identify the mode of control of the MAC that is important for pathogen complement evasion.},
  author       = {Singh, Birendra and Jalalvand, Farshid and Mörgelin, Matthias and Zipfel, Peter and Blom, Anna and Riesbeck, Kristian},
  issn         = {1365-2958},
  language     = {eng},
  pages        = {80--98},
  publisher    = {Wiley-Blackwell},
  series       = {Molecular Microbiology},
  title        = {Haemophilus influenzae protein E recognizes the C-terminal domain of vitronectin and modulates the membrane attack complex.},
  url          = {http://dx.doi.org/10.1111/j.1365-2958.2011.07678.x},
  volume       = {81},
  year         = {2011},
}