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Haemophilus influenzae acquires vitronectin via the ubiquitous Protein F to subvert host innate immunity.

Su, Yu-Ching LU ; Jalalvand, Farshid LU ; Mörgelin, Matthias LU ; Blom, Anna LU orcid ; Singh, Birendra LU and Riesbeck, Kristian LU orcid (2013) In Molecular Microbiology 87(6). p.1245-1266
Abstract
Acquisition of the complement inhibitor vitronectin (Vn) is important for the respiratory tract pathogen nontypeable Haemophilus influenzae (NTHi) to escape complement-mediated killing. NTHi actively recruits Vn, and we previously showed that this interaction involves Protein E (PE). Here we describe a second Vn-binding protein, a 30 kDa Yersinia YfeA homologue designated as Protein F (PF). An isogenic NTHi 3655Δhpf mutant devoid of PF displayed a reduced binding of Vn, and was consequently more sensitive to killing by human serum compared with the wild type. Surface expression of PF on Escherichia coli conferred binding of Vn that resulted in a serum resistant phenotype. Molecular analyses revealed that the N-terminal of PF (Lys23-Glu48)... (More)
Acquisition of the complement inhibitor vitronectin (Vn) is important for the respiratory tract pathogen nontypeable Haemophilus influenzae (NTHi) to escape complement-mediated killing. NTHi actively recruits Vn, and we previously showed that this interaction involves Protein E (PE). Here we describe a second Vn-binding protein, a 30 kDa Yersinia YfeA homologue designated as Protein F (PF). An isogenic NTHi 3655Δhpf mutant devoid of PF displayed a reduced binding of Vn, and was consequently more sensitive to killing by human serum compared with the wild type. Surface expression of PF on Escherichia coli conferred binding of Vn that resulted in a serum resistant phenotype. Molecular analyses revealed that the N-terminal of PF (Lys23-Glu48) bound to the C-terminal of Vn (Phe352-Ser374) without disrupting the inhibitory role of Vn on the membrane attack complex. The PF-Vn complex actively delayed C9 deposition on PF-expressing bacteria. Comparative studies of binding affinity and multiple mutants demonstrated that both PE and PF contribute individually to NTHi serum survival. PF was highly conserved and ubiquitously expressed in a series of randomly selected NTHi clinical isolates (n = 18). In conclusion, the multifaceted binding of Vn is beneficial for NTHi survival in serum and may contribute to successful colonization and consequently infection. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Bacterial Proteins/genetics, Blood Bactericidal Activity, Gene Deletion, Haemophilus influenzae/genetics, Humans, Immune Evasion, Immunity, Innate, Microbial Viability, Protein Binding, Protein Interaction Mapping, Vitronectin/metabolism
in
Molecular Microbiology
volume
87
issue
6
pages
1245 - 1266
publisher
Wiley-Blackwell
external identifiers
  • wos:000316221200009
  • pmid:23387957
  • scopus:84875000681
  • pmid:23387957
ISSN
1365-2958
DOI
10.1111/mmi.12164
language
English
LU publication?
yes
id
39b3aff8-7af3-472e-b9a3-1763c0339965 (old id 3560110)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/23387957?dopt=Abstract
date added to LUP
2016-04-01 10:46:27
date last changed
2022-01-26 02:21:16
@article{39b3aff8-7af3-472e-b9a3-1763c0339965,
  abstract     = {{Acquisition of the complement inhibitor vitronectin (Vn) is important for the respiratory tract pathogen nontypeable Haemophilus influenzae (NTHi) to escape complement-mediated killing. NTHi actively recruits Vn, and we previously showed that this interaction involves Protein E (PE). Here we describe a second Vn-binding protein, a 30 kDa Yersinia YfeA homologue designated as Protein F (PF). An isogenic NTHi 3655Δhpf mutant devoid of PF displayed a reduced binding of Vn, and was consequently more sensitive to killing by human serum compared with the wild type. Surface expression of PF on Escherichia coli conferred binding of Vn that resulted in a serum resistant phenotype. Molecular analyses revealed that the N-terminal of PF (Lys23-Glu48) bound to the C-terminal of Vn (Phe352-Ser374) without disrupting the inhibitory role of Vn on the membrane attack complex. The PF-Vn complex actively delayed C9 deposition on PF-expressing bacteria. Comparative studies of binding affinity and multiple mutants demonstrated that both PE and PF contribute individually to NTHi serum survival. PF was highly conserved and ubiquitously expressed in a series of randomly selected NTHi clinical isolates (n = 18). In conclusion, the multifaceted binding of Vn is beneficial for NTHi survival in serum and may contribute to successful colonization and consequently infection.}},
  author       = {{Su, Yu-Ching and Jalalvand, Farshid and Mörgelin, Matthias and Blom, Anna and Singh, Birendra and Riesbeck, Kristian}},
  issn         = {{1365-2958}},
  keywords     = {{Bacterial Proteins/genetics; Blood Bactericidal Activity; Gene Deletion; Haemophilus influenzae/genetics; Humans; Immune Evasion; Immunity, Innate; Microbial Viability; Protein Binding; Protein Interaction Mapping; Vitronectin/metabolism}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1245--1266}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Molecular Microbiology}},
  title        = {{Haemophilus influenzae acquires vitronectin via the ubiquitous Protein F to subvert host innate immunity.}},
  url          = {{http://dx.doi.org/10.1111/mmi.12164}},
  doi          = {{10.1111/mmi.12164}},
  volume       = {{87}},
  year         = {{2013}},
}