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Nontypeable haemophilus influenzae P5 binds human C4b-binding protein, promoting serum resistance

Thofte, Oskar LU orcid ; Bettoni, Serena LU orcid ; Su, Yu Ching LU ; Thegerström, John LU ; Jonsson, Sandra LU orcid ; Mattsson, Emma LU ; Sandblad, Linda ; Martı, Sara ; Garmendia, Junkal and Blom, Anna M. LU orcid , et al. (2021) In Journal of Immunology 207(6). p.1566-1577
Abstract

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP... (More)

Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP binding and consequently increased serum resistance. Moreover, P5 expression was positively correlated with C4BP binding in a series of clinical isolates. We revealed higher levels of P5 surface expression and consequently more C4BP binding in isolates from the lower respiratory tract of chronic obstructive pulmonary disease patients and tonsil specimens compared with isolates from the upper respiratory tract and the bloodstream (invasive strains). Our results highlight P5 as an important protein for protecting NTHi against complement-mediated killing.

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type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
207
issue
6
pages
12 pages
publisher
American Association of Immunologists
external identifiers
  • scopus:85114615267
  • pmid:34433620
ISSN
0022-1767
DOI
10.4049/jimmunol.2100105
language
English
LU publication?
yes
id
3c8a7011-5278-4d1b-9897-8809634cb9de
date added to LUP
2021-10-08 14:19:30
date last changed
2024-06-15 17:44:38
@article{3c8a7011-5278-4d1b-9897-8809634cb9de,
  abstract     = {{<p>Nontypeable Haemophilus influenzae (NTHi) is a Gram-negative human pathogen that causes infections mainly in the upper and lower respiratory tract. The bacterium is associated with bronchitis and exacerbations in patients suffering from chronic obstructive pulmonary disease and frequently causes acute otitis media in preschool children. We have previously demonstrated that the binding of C4b binding protein (C4BP) is important for NTHi complement evasion. In this study, we identified outer membrane protein 5 (P5) of NTHi as a novel ligand of C4BP. Importantly, we observed significantly lower C4BP binding and decreased serum resistance in P5-deficient NTHi mutants. Surface expression of recombinant P5 on Escherichia coli conferred C4BP binding and consequently increased serum resistance. Moreover, P5 expression was positively correlated with C4BP binding in a series of clinical isolates. We revealed higher levels of P5 surface expression and consequently more C4BP binding in isolates from the lower respiratory tract of chronic obstructive pulmonary disease patients and tonsil specimens compared with isolates from the upper respiratory tract and the bloodstream (invasive strains). Our results highlight P5 as an important protein for protecting NTHi against complement-mediated killing.</p>}},
  author       = {{Thofte, Oskar and Bettoni, Serena and Su, Yu Ching and Thegerström, John and Jonsson, Sandra and Mattsson, Emma and Sandblad, Linda and Martı, Sara and Garmendia, Junkal and Blom, Anna M. and Riesbeck, Kristian}},
  issn         = {{0022-1767}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{6}},
  pages        = {{1566--1577}},
  publisher    = {{American Association of Immunologists}},
  series       = {{Journal of Immunology}},
  title        = {{Nontypeable haemophilus influenzae P5 binds human C4b-binding protein, promoting serum resistance}},
  url          = {{http://dx.doi.org/10.4049/jimmunol.2100105}},
  doi          = {{10.4049/jimmunol.2100105}},
  volume       = {{207}},
  year         = {{2021}},
}