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Transcriptional Regulator FabR Is Associated with the Virulence of Non-typeable Haemophilus influenzae in Host-Pathogen Interactions

Janoušková, Martina LU ; Su, Yu-Ching LU ; Jonsson, Sandra LU orcid ; Rao, Vaishnavi Venkatesh LU ; Dalence, Silvana LU ; Végvári, Ákos LU ; Zubarev, Roman A ; Žáček, Petr ; Håkansson, Anders P LU orcid and Resman, Fredrik LU , et al. (2026) In The Journal of infectious diseases
Abstract

BACKGROUND: Regulation of transcription is essential for the pathoadaptation of non-typeable Haemophilus influenzae(NTHi). We identified FabR as a previously unrecognized transcriptional regulator in NTHi through its binding to the promoter region of ompP5 and investigated its contribution to bacterial virulence and physiology.

METHODS: A fabR deletion mutant (ΔfabR) was generated in NTHi strain 3655. The mutant was compared with the wild-type strain in assays of host cell adherence, serum resistance, immunoglobulin G (IgG) deposition, vitronectin binding, murine nasopharyngeal colonization, protein expression, membrane fatty acid composition, and metabolic activity. Metabolic activity was also evaluated in ΔfabR mutants generated... (More)

BACKGROUND: Regulation of transcription is essential for the pathoadaptation of non-typeable Haemophilus influenzae(NTHi). We identified FabR as a previously unrecognized transcriptional regulator in NTHi through its binding to the promoter region of ompP5 and investigated its contribution to bacterial virulence and physiology.

METHODS: A fabR deletion mutant (ΔfabR) was generated in NTHi strain 3655. The mutant was compared with the wild-type strain in assays of host cell adherence, serum resistance, immunoglobulin G (IgG) deposition, vitronectin binding, murine nasopharyngeal colonization, protein expression, membrane fatty acid composition, and metabolic activity. Metabolic activity was also evaluated in ΔfabR mutants generated in additional NTHi strains.

RESULTS: Deletion of fabR reduced host cell adherence, increased serum sensitivity, enhanced IgG deposition, and decreased vitronectin binding compared with the wild-type strain. The ΔfabR mutant also exhibited impaired colonization of the murine nasopharynx. Proteomic analyses demonstrated altered expression of metabolic proteins, accompanied by an increased unsaturated-to-saturated fatty acid ratio. Furthermore, ΔfabR mutants from multiple NTHi strains showed increased metabolic activity, indicating a conserved role for FabR in metabolic regulation.

CONCLUSIONS: FabR is a novel transcriptional regulator that may contribute to NTHi virulence. By modulating bacterial metabolism and membrane lipid composition, FabR may influence outer membrane architecture, thereby affecting host interaction, immune evasion, and colonization.

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organization
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type
Contribution to journal
publication status
epub
subject
in
The Journal of infectious diseases
article number
jiag419
publisher
Oxford University Press
external identifiers
  • pmid:42594159
ISSN
1537-6613
DOI
10.1093/infdis/jiag419
language
English
LU publication?
yes
additional info
© The Author(s) 2026. Published by Oxford University Press on behalf of Infectious Diseases Society of America.
id
e5e97aee-4aa6-4d79-8091-a42d3a2547f3
date added to LUP
2026-10-12 07:59:33
date last changed
2026-10-12 08:10:29
@article{e5e97aee-4aa6-4d79-8091-a42d3a2547f3,
  abstract     = {{<p>BACKGROUND: Regulation of transcription is essential for the pathoadaptation of non-typeable Haemophilus influenzae(NTHi). We identified FabR as a previously unrecognized transcriptional regulator in NTHi through its binding to the promoter region of ompP5 and investigated its contribution to bacterial virulence and physiology.</p><p>METHODS: A fabR deletion mutant (ΔfabR) was generated in NTHi strain 3655. The mutant was compared with the wild-type strain in assays of host cell adherence, serum resistance, immunoglobulin G (IgG) deposition, vitronectin binding, murine nasopharyngeal colonization, protein expression, membrane fatty acid composition, and metabolic activity. Metabolic activity was also evaluated in ΔfabR mutants generated in additional NTHi strains.</p><p>RESULTS: Deletion of fabR reduced host cell adherence, increased serum sensitivity, enhanced IgG deposition, and decreased vitronectin binding compared with the wild-type strain. The ΔfabR mutant also exhibited impaired colonization of the murine nasopharynx. Proteomic analyses demonstrated altered expression of metabolic proteins, accompanied by an increased unsaturated-to-saturated fatty acid ratio. Furthermore, ΔfabR mutants from multiple NTHi strains showed increased metabolic activity, indicating a conserved role for FabR in metabolic regulation.</p><p>CONCLUSIONS: FabR is a novel transcriptional regulator that may contribute to NTHi virulence. By modulating bacterial metabolism and membrane lipid composition, FabR may influence outer membrane architecture, thereby affecting host interaction, immune evasion, and colonization.</p>}},
  author       = {{Janoušková, Martina and Su, Yu-Ching and Jonsson, Sandra and Rao, Vaishnavi Venkatesh and Dalence, Silvana and Végvári, Ákos and Zubarev, Roman A and Žáček, Petr and Håkansson, Anders P and Resman, Fredrik and Riesbeck, Kristian}},
  issn         = {{1537-6613}},
  language     = {{eng}},
  month        = {{08}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of infectious diseases}},
  title        = {{Transcriptional Regulator FabR Is Associated with the Virulence of Non-typeable Haemophilus influenzae in Host-Pathogen Interactions}},
  url          = {{http://dx.doi.org/10.1093/infdis/jiag419}},
  doi          = {{10.1093/infdis/jiag419}},
  year         = {{2026}},
}