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:
https://lup.lub.lu.se/record/1477258
- author
- Hallström, Teresia
LU
; Blom, Anna
LU
; Zipfel, Peter F.
and Riesbeck, Kristian
LU
- organization
- publishing date
- 2009
- 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
- pmid:19635912
- 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
- 2016-04-01 13:16:23
- date last changed
- 2022-01-27 18:18:43
@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}},
doi = {{10.4049/jimmunol.0803226}},
volume = {{183}},
year = {{2009}},
}