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The Emerging Pathogen Non-typeable Haemophilus influenzae : Roles of EF-Tu and P5 in Host-pathogen Interactions

Thofte, Oskar LU orcid (2025) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
Non-typeable Haemophilus influenzae (NTHi) is an emerging respiratory pathogen that causes a significant disease burden worldwide, yet an effective vaccine is still lacking. The focus of this thesis is to elucidate the critical molecular interactions governing NTHi pathogenesis and host immunity. We identified Elongation Factor Tu (EF-Tu) as a surface-exposed protein on NTHi, demonstrating its immunogenicity and potential as a vaccine candidate by showing that anti-EF-Tu antibodies mediate bacterial killing and provide protection in preclinical models. Concurrently, we uncovered a novel role for the innate receptor Dectin-1 in defence against bacterial pneumonia – a finding supported by human genetic associations and mouse infection... (More)
Non-typeable Haemophilus influenzae (NTHi) is an emerging respiratory pathogen that causes a significant disease burden worldwide, yet an effective vaccine is still lacking. The focus of this thesis is to elucidate the critical molecular interactions governing NTHi pathogenesis and host immunity. We identified Elongation Factor Tu (EF-Tu) as a surface-exposed protein on NTHi, demonstrating its immunogenicity and potential as a vaccine candidate by showing that anti-EF-Tu antibodies mediate bacterial killing and provide protection in preclinical models. Concurrently, we uncovered a novel role for the innate receptor Dectin-1 in defence against bacterial pneumonia – a finding supported by human genetic associations and mouse infection studies and identifying bacterial EF-Tu as its conserved ligand. Complementing these findings, we identified Outer Membrane Protein P5 (OMP P5) as the key NTHi factor mediating recruitment of the human complement inhibitor C4BP, establishing a crucial mechanism for NTHi immune evasion and serum resistance. This research advances our understanding of specific bacterial molecules (EF-Tu, P5) and host pathways (Dectin-1) central to NTHi infection, and possibly important for future vaccines and therapeutics against this pathogen. (Less)
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author
supervisor
opponent
  • Professor Nyunt Wai, Sun, Department of Molecular Biology, Umeå University
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Non-typeable Haemophilus influenzae (NTHi), Elongation Factor Tu (EF-Tu), Dectin-1, Outer Membrane Protein P5 (OMP P5), C4b-Binding Protein (C4BP), complement evasion, bacterial pneumonia
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2025:67
pages
102 pages
publisher
Lund University, Faculty of Medicine
defense location
Agardh föreläsningssal, CRC, Jan Waldenströms gata 35, Skånes Universitetssjukhus i Malmö
defense date
2025-06-05 13:15:00
ISSN
1652
ISBN
978-91-8021-720-0
language
English
LU publication?
yes
id
7eeeb7ce-ea6c-41c7-aac4-230baffd6c9c
date added to LUP
2025-05-14 16:03:12
date last changed
2025-05-15 12:41:01
@phdthesis{7eeeb7ce-ea6c-41c7-aac4-230baffd6c9c,
  abstract     = {{Non-typeable Haemophilus influenzae (NTHi) is an emerging respiratory pathogen that causes a significant disease burden worldwide, yet an effective vaccine is still lacking. The focus of this thesis is to elucidate the critical molecular interactions governing NTHi pathogenesis and host immunity. We identified Elongation Factor Tu (EF-Tu) as a surface-exposed protein on NTHi, demonstrating its immunogenicity and potential as a vaccine candidate by showing that anti-EF-Tu antibodies mediate bacterial killing and provide protection in preclinical models. Concurrently, we uncovered a novel role for the innate receptor Dectin-1 in defence against bacterial pneumonia – a finding supported by human genetic associations and mouse infection studies and identifying bacterial EF-Tu as its conserved ligand. Complementing these findings, we identified Outer Membrane Protein P5 (OMP P5) as the key NTHi factor mediating recruitment of the human complement inhibitor C4BP, establishing a crucial mechanism for NTHi immune evasion and serum resistance. This research advances our understanding of specific bacterial molecules (EF-Tu, P5) and host pathways (Dectin-1) central to NTHi infection, and possibly important for future vaccines and therapeutics against this pathogen.}},
  author       = {{Thofte, Oskar}},
  isbn         = {{978-91-8021-720-0}},
  issn         = {{1652}},
  keywords     = {{Non-typeable Haemophilus influenzae (NTHi); Elongation Factor Tu (EF-Tu); Dectin-1; Outer Membrane Protein P5 (OMP P5); C4b-Binding Protein (C4BP); complement evasion; bacterial pneumonia}},
  language     = {{eng}},
  number       = {{2025:67}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{The Emerging Pathogen Non-typeable Haemophilus influenzae : Roles of EF-Tu and P5 in Host-pathogen Interactions}},
  year         = {{2025}},
}