ArticleInfection and immunity2006
Complex role of hemoglobin and hemoglobin-haptoglobin binding proteins in Haemophilus influenzae virulence in the infant rat model of invasive infection.
Article in Infection and immunity, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Decoding the spatiotemporal heterogeneity of bacterial virulence gene expression using single-cell approaches.Frontiers in microbiology · 2026Review
- Exploiting haem-iron dependence of nontypeableFrontiers in cellular and infection microbiology · 2025Review
- Phasevarions inMicrobiology spectrum · 2024Article
- Examination of phase-variable haemoglobin-haptoglobin binding proteins in non-typeable Haemophilus influenzae reveals a diverse distribution of multiple variants.FEMS microbiology letters · 2022Article
- Review of immunological plasma markers for longitudinal analysis of inflammation and infection in rat models.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2022Review
- Haemophilin-Producing Strains ofPathogens (Basel, Switzerland) · 2021Article
- In Vitro Anti-NTHi Activity of Haemophilin-Producing Strains ofPathogens (Basel, Switzerland) · 2020Article
- Moonlighting of Haemophilus influenzae heme acquisition systems contributes to the host airway-pathogen interplay in a coordinated manner.Virulence · 2019Article
- Heme Synthesis and Acquisition in Bacterial Pathogens.Journal of molecular biology · 2016Review
- Structural basis for haem piracy from host haemopexin by Haemophilus influenzae.Nature communications · 2016Article
- Draft Genome Sequences of Six Nontypeable Haemophilus influenzae Strains That Establish Bacteremia in the Infant Rat Model of Invasive Disease.Genome announcements · 2015Article
- A biphasic epigenetic switch controls immunoevasion, virulence and niche adaptation in non-typeable Haemophilus influenzae.Nature communications · 2015Article
- Antisera Against Certain Conserved Surface-Exposed Peptides of Nontypeable Haemophilus influenzae Are Protective.PloS one · 2015Article
- The role of the RNA chaperone Hfq in Haemophilus influenzae pathogenesis.BMC microbiology · 2013Article
- Shared and distinct mechanisms of iron acquisition by bacterial and fungal pathogens of humans.Frontiers in cellular and infection microbiology · 2013Review
- Signature-tagging of a bacterial isolate demonstrates phenotypic variability of the progeny in vivo in the absence of defined mutations.Journal of microbiological methods · 2012Article
- A functional tonB gene is required for both virulence and competitive fitness in a chinchilla model of Haemophilus influenzae otitis media.BMC research notes · 2012Article
- Nontypeable Haemophilus influenzae genetic islands associated with chronic pulmonary infection.PloS one · 2012Article
- Haemophilus influenzae OxyR: characterization of its regulation, regulon and role in fitness.PloS one · 2012Article
- The structure of the first representative of Pfam family PF09836 reveals a two-domain organization and suggests involvement in transcriptional regulation.Acta crystallographica. Section F, Structural biology and crystallization communications · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Haemophilus influenzae requires an exogenous heme source for aerobic growth in vitro. Hemoglobin or hemoglobin-haptoglobin satisfies this requirement. Heme acquisition from hemoglobin-haptoglobin is mediated by proteins encoded by hgp genes. Both Hgps and additional proteins, including those encoded by the hxu operon, provide independent pathways for hemoglobin utilization. Recently we showed that deletion of the set of three hgp genes from a nontypeable strain (86-028NP) of H. influenzae attenuated virulence in the chinchilla otitis media model of noninvasive disease. The present study was undertaken to investigate the role of the hgp genes in virulence of the wild-type serotype b clinical isolate HI689 in the infant rat model of hematogenous meningitis, an established model of invasive disease requiring aerobic growth. Bacteremia of high titer and long duration (>14 days) and histopathologically confirmed meningitis occurred in >95% of infant rats challenged at 5 days of age with strain HI689. While mutations disrupting either the Hgp- or Hxu-mediated pathway of heme acquisition had no effect on virulence in infant rats, an isogenic mutant deficient for both pathways was unable to sustain bacteremia or produce meningitis. In contrast, mutations disrupting either pathway decreased the limited ability of H. influenzae to initiate and sustain bacteremia in weanling rats. Biochemical and growth studies also indicated that infant rat plasma contains multiple heme sources that change with age. Taken together, these data indicate that both the hgp genes and the hxuC gene are virulence determinants in the rat model of human invasive disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.