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The Major Outer Membrane Protein P5 Binds Vitronectin to Mediate Serum Resistance in Nontypeable Haemophilus influenzae

Jonsson, Sandra LU orcid ; Janoušková, Martina LU ; Venkatesh Rao, Vaishnavi LU ; Garmendia, Junkal ; Su, Yu Ching LU and Riesbeck, Kristian LU orcid (2025) In Journal of Infectious Diseases 232(6). p.981-991
Abstract

Acquisition of complement regulators is a virulence strategy used by nontypeable Haemophilus influenzae (NTHi) to evade complement-mediated killing by the host. The major outer membrane protein of NTHi, P5, binds C4b-binding protein and factor H to promote bacterial serum resistance. We show that P5 also binds vitronectin, which inhibits the formation of the membrane attack complex at the terminal stage of the complement pathway. Heterologous surface expression of P5 variants from NTHi strains 3655, KR271, KR317, and P652 promoted vitronectin binding to the P5-expressing Escherichia coli. In contrast, deletion of P5 from the NTHi strains reduced vitronectin binding. Vitronectin acquisition conferred serum resistance to P5-expressing E.... (More)

Acquisition of complement regulators is a virulence strategy used by nontypeable Haemophilus influenzae (NTHi) to evade complement-mediated killing by the host. The major outer membrane protein of NTHi, P5, binds C4b-binding protein and factor H to promote bacterial serum resistance. We show that P5 also binds vitronectin, which inhibits the formation of the membrane attack complex at the terminal stage of the complement pathway. Heterologous surface expression of P5 variants from NTHi strains 3655, KR271, KR317, and P652 promoted vitronectin binding to the P5-expressing Escherichia coli. In contrast, deletion of P5 from the NTHi strains reduced vitronectin binding. Vitronectin acquisition conferred serum resistance to P5-expressing E. coli, but not to NTHi ΔompP5 mutants. Using site-directed mutagenesis, extracellular loop 2 of the P5 variants was identified as the binding site for vitronectin. In conclusion, our findings highlight P5 as a receptor for vitronectin that promotes NTHi serum resistance.

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; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
complement inhibitor, nontypeable Haemophilus influenzae, OMP P5, serum resistance, vitronectin
in
Journal of Infectious Diseases
volume
232
issue
6
pages
981 - 991
publisher
Oxford University Press
external identifiers
  • scopus:105025437889
  • pmid:40977539
ISSN
0022-1899
DOI
10.1093/infdis/jiaf489
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
id
c847160a-e73b-4a0a-99bc-c15501f1ecc6
date added to LUP
2026-02-11 14:15:54
date last changed
2026-02-12 03:00:56
@article{c847160a-e73b-4a0a-99bc-c15501f1ecc6,
  abstract     = {{<p>Acquisition of complement regulators is a virulence strategy used by nontypeable Haemophilus influenzae (NTHi) to evade complement-mediated killing by the host. The major outer membrane protein of NTHi, P5, binds C4b-binding protein and factor H to promote bacterial serum resistance. We show that P5 also binds vitronectin, which inhibits the formation of the membrane attack complex at the terminal stage of the complement pathway. Heterologous surface expression of P5 variants from NTHi strains 3655, KR271, KR317, and P652 promoted vitronectin binding to the P5-expressing Escherichia coli. In contrast, deletion of P5 from the NTHi strains reduced vitronectin binding. Vitronectin acquisition conferred serum resistance to P5-expressing E. coli, but not to NTHi ΔompP5 mutants. Using site-directed mutagenesis, extracellular loop 2 of the P5 variants was identified as the binding site for vitronectin. In conclusion, our findings highlight P5 as a receptor for vitronectin that promotes NTHi serum resistance.</p>}},
  author       = {{Jonsson, Sandra and Janoušková, Martina and Venkatesh Rao, Vaishnavi and Garmendia, Junkal and Su, Yu Ching and Riesbeck, Kristian}},
  issn         = {{0022-1899}},
  keywords     = {{complement inhibitor; nontypeable Haemophilus influenzae; OMP P5; serum resistance; vitronectin}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{6}},
  pages        = {{981--991}},
  publisher    = {{Oxford University Press}},
  series       = {{Journal of Infectious Diseases}},
  title        = {{The Major Outer Membrane Protein P5 Binds Vitronectin to Mediate Serum Resistance in Nontypeable Haemophilus influenzae}},
  url          = {{http://dx.doi.org/10.1093/infdis/jiaf489}},
  doi          = {{10.1093/infdis/jiaf489}},
  volume       = {{232}},
  year         = {{2025}},
}