Haemophilus influenzae Uses the Surface Protein E To Acquire Human Plasminogen and To Evade Innate Immunity
Barthel, Diana ; Singh, Birendra LU ; Riesbeck, Kristian LU
and Zipfel, Peter F.
(2012)
In Journal of Immunology
188(1).
p.379-385
- Abstract
- Pathogenic microbes acquire the human plasma protein plasminogen to their surface. In this article, we characterize binding of this important coagulation regulator to the respiratory pathogen nontypeable Haemophilus influenzae and identify the Haemophilus surface protein E (PE) as a new plasminogen-binding protein. Plasminogen binds dose dependently to intact bacteria and to purified PE. The plasminogen-PE interaction is mediated by lysine residues and is also affected by ionic strength. The H. influenzae PE knockout strain (nontypeable H. influenzae 3655 Delta pe) bound plasminogen with similar to 65% lower intensity as compared with the wild-type, PE-expressing strain. In addition, PE expressed ectopically on the surface of Escherichia... (More)
- Pathogenic microbes acquire the human plasma protein plasminogen to their surface. In this article, we characterize binding of this important coagulation regulator to the respiratory pathogen nontypeable Haemophilus influenzae and identify the Haemophilus surface protein E (PE) as a new plasminogen-binding protein. Plasminogen binds dose dependently to intact bacteria and to purified PE. The plasminogen-PE interaction is mediated by lysine residues and is also affected by ionic strength. The H. influenzae PE knockout strain (nontypeable H. influenzae 3655 Delta pe) bound plasminogen with similar to 65% lower intensity as compared with the wild-type, PE-expressing strain. In addition, PE expressed ectopically on the surface of Escherichia coli also bound plasminogen. Plasminogen, either attached to intact H. influenzae or bound to PE, was accessible for urokinase plasminogen activator. The converted active plasmin cleaved the synthetic substrate S-2251, and the natural substrates fibrinogen and C3b. Using synthetic peptides that cover the complete sequence of the PE protein, the major plasminogen-binding region was localized to a linear 28-aa-long N-terminal peptide, which represents aa 41-68. PE binds plasminogen and also vitronectin, and the two human plasma proteins compete for PE binding. Thus, PE is a major plasminogen-binding protein of the Gram-negative bacterium H. influenzae, and when converted to plasmin, PE-bound plasmin aids in immune evasion and contributes to bacterial virulence. The Journal of Immunology, 2012, 188: 379-385. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2362657
- author
- Barthel, Diana
; Singh, Birendra
LU
; Riesbeck, Kristian
LU
and Zipfel, Peter F.
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 188
- issue
- 1
- pages
- 379 - 385
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000298628400044
- scopus:84855366615
- pmid:22124123
- ISSN
- 1550-6606
- DOI
- 10.4049/jimmunol.1101927
- language
- English
- LU publication?
- yes
- id
- 0b65cb53-7d04-447a-8c20-d925b0de72c0 (old id 2362657)
- date added to LUP
- 2016-04-01 15:02:40
- date last changed
- 2022-03-06 22:25:52
@misc{0b65cb53-7d04-447a-8c20-d925b0de72c0,
abstract = {{Pathogenic microbes acquire the human plasma protein plasminogen to their surface. In this article, we characterize binding of this important coagulation regulator to the respiratory pathogen nontypeable Haemophilus influenzae and identify the Haemophilus surface protein E (PE) as a new plasminogen-binding protein. Plasminogen binds dose dependently to intact bacteria and to purified PE. The plasminogen-PE interaction is mediated by lysine residues and is also affected by ionic strength. The H. influenzae PE knockout strain (nontypeable H. influenzae 3655 Delta pe) bound plasminogen with similar to 65% lower intensity as compared with the wild-type, PE-expressing strain. In addition, PE expressed ectopically on the surface of Escherichia coli also bound plasminogen. Plasminogen, either attached to intact H. influenzae or bound to PE, was accessible for urokinase plasminogen activator. The converted active plasmin cleaved the synthetic substrate S-2251, and the natural substrates fibrinogen and C3b. Using synthetic peptides that cover the complete sequence of the PE protein, the major plasminogen-binding region was localized to a linear 28-aa-long N-terminal peptide, which represents aa 41-68. PE binds plasminogen and also vitronectin, and the two human plasma proteins compete for PE binding. Thus, PE is a major plasminogen-binding protein of the Gram-negative bacterium H. influenzae, and when converted to plasmin, PE-bound plasmin aids in immune evasion and contributes to bacterial virulence. The Journal of Immunology, 2012, 188: 379-385.}},
author = {{Barthel, Diana and Singh, Birendra and Riesbeck, Kristian and Zipfel, Peter F.}},
issn = {{1550-6606}},
language = {{eng}},
number = {{1}},
pages = {{379--385}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{Haemophilus influenzae Uses the Surface Protein E To Acquire Human Plasminogen and To Evade Innate Immunity}},
url = {{http://dx.doi.org/10.4049/jimmunol.1101927}},
doi = {{10.4049/jimmunol.1101927}},
volume = {{188}},
year = {{2012}},
}