Haemophilus influenzae uses the surface protein E to acquire human plasminogen and to evade innate immunity.
J Immunol
; 188(1): 379-85, 2012 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-22124123
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 3655Δpe) bound plasminogen with â¼65% 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Plasminogênio
/
Proteínas da Membrana Bacteriana Externa
/
Haemophilus influenzae
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Fatores de Virulência
/
Evasão da Resposta Imune
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Infecções por Haemophilus
/
Imunidade Inata
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha