Advanced

Nontypeable Haemophilus influenzae Protein E Binds Vitronectin and Is Important for Serum Resistance

Hallström, Teresia LU ; Blom, Anna LU ; Zipfel, Peter F. and Riesbeck, Kristian LU (2009) In Journal of Immunology 183(4). p.2593-2601
Abstract
Nontypeable Haemophilus influenzae (NTHi) commonly causes local disease in the upper and lower respiratory tract and has recently been shown to interfere with both the classical and alternative pathways of complement activation. The terminal pathway of the complement system is regulated by vitronectin that is a component of both plasma and the extracellular matrix. In this study, we identify protein E (PE; 16 kDa), which is a recently characterized ubiquitous outer membrane protein, as a vitronectin-binding protein of NTHi. A PE-deficient NTHi mutant had a markedly reduced survival in serum compared with the PE-expressing isogenic NTHi wild type. Moreover, the PE-deficient mutant showed a significantly decreased binding to both soluble and... (More)
Nontypeable Haemophilus influenzae (NTHi) commonly causes local disease in the upper and lower respiratory tract and has recently been shown to interfere with both the classical and alternative pathways of complement activation. The terminal pathway of the complement system is regulated by vitronectin that is a component of both plasma and the extracellular matrix. In this study, we identify protein E (PE; 16 kDa), which is a recently characterized ubiquitous outer membrane protein, as a vitronectin-binding protein of NTHi. A PE-deficient NTHi mutant had a markedly reduced survival in serum compared with the PE-expressing isogenic NTHi wild type. Moreover, the PE-deficient mutant showed a significantly decreased binding to both soluble and immobilized vitronectin. In parallel, PE-expressing Escherichia coli bound soluble vitronectin and adhered to immobilized vitronectin compared with controls. Surface plasmon resonance technology revealed a K-D of 0.4 mu M for the interaction between recombinant PE and immobilized vitronectin. Moreover, the PE-dependent vitronectin-binding site was located at the heparin-binding domains of vitronectin and the major vitronectin-binding domain was found in the central core of PE (aa 84-108). Importantly, vitronectin bound to the surface of NTHi 3655 reduced membrane attack complex-induced hemolysis. In contrast to incubation with normal human serum, NTHi 3655 showed a reduced survival in vitronectin-depleted human serum, thus demonstrating that vitronectin mediates a protective role at the bacteria] surface. Our findings show that PE, by binding vitronectin, may play an important role in NTHi pathogenesis. The Journal of Immunology, 2009, 183: 2593-2601. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
183
issue
4
pages
2593 - 2601
publisher
American Association of Immunologists
external identifiers
  • wos:000268906500047
  • scopus:70149120375
ISSN
1550-6606
DOI
10.4049/jimmunol.0803226
language
English
LU publication?
yes
id
a2ab6767-ca6c-4527-8f1e-217da06cea72 (old id 1477258)
date added to LUP
2009-09-23 13:14:17
date last changed
2017-08-27 04:35:25
@article{a2ab6767-ca6c-4527-8f1e-217da06cea72,
  abstract     = {Nontypeable Haemophilus influenzae (NTHi) commonly causes local disease in the upper and lower respiratory tract and has recently been shown to interfere with both the classical and alternative pathways of complement activation. The terminal pathway of the complement system is regulated by vitronectin that is a component of both plasma and the extracellular matrix. In this study, we identify protein E (PE; 16 kDa), which is a recently characterized ubiquitous outer membrane protein, as a vitronectin-binding protein of NTHi. A PE-deficient NTHi mutant had a markedly reduced survival in serum compared with the PE-expressing isogenic NTHi wild type. Moreover, the PE-deficient mutant showed a significantly decreased binding to both soluble and immobilized vitronectin. In parallel, PE-expressing Escherichia coli bound soluble vitronectin and adhered to immobilized vitronectin compared with controls. Surface plasmon resonance technology revealed a K-D of 0.4 mu M for the interaction between recombinant PE and immobilized vitronectin. Moreover, the PE-dependent vitronectin-binding site was located at the heparin-binding domains of vitronectin and the major vitronectin-binding domain was found in the central core of PE (aa 84-108). Importantly, vitronectin bound to the surface of NTHi 3655 reduced membrane attack complex-induced hemolysis. In contrast to incubation with normal human serum, NTHi 3655 showed a reduced survival in vitronectin-depleted human serum, thus demonstrating that vitronectin mediates a protective role at the bacteria] surface. Our findings show that PE, by binding vitronectin, may play an important role in NTHi pathogenesis. The Journal of Immunology, 2009, 183: 2593-2601.},
  author       = {Hallström, Teresia and Blom, Anna and Zipfel, Peter F. and Riesbeck, Kristian},
  issn         = {1550-6606},
  language     = {eng},
  number       = {4},
  pages        = {2593--2601},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Nontypeable Haemophilus influenzae Protein E Binds Vitronectin and Is Important for Serum Resistance},
  url          = {http://dx.doi.org/10.4049/jimmunol.0803226},
  volume       = {183},
  year         = {2009},
}