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Updated: May 17, 2026

Assessing Respiratory Immune Responses to Haemophilus Influenzae
Published on: June 29, 2021
Haemophilus parainfluenzae has a limited core lipopolysaccharide repertoire with no phase variation
Rosanna E B Young1, Derek W Hood
1Department of Paediatrics, University of Oxford, Oxford, UK. r.young@ucl.ac.uk
Abstract:
Cell surface lipopolysaccharide (LPS) is a well characterized virulence determinant for the human pathogen Haemophilus influenzae, so an investigation of LPS in the less pathogenic Haemophilus parainfluenzae could yield important insights. Using a panel of 18 commensal H. parainfluenzae isolates we demonstrate that the set of genes for inner core LPS biosynthesis largely resembles that of H. influenzae, with an additional heptosyltransferase I gene similar to waaC from Pasteurella multocida. Inner core LPS structure is therefore likely to be largely conserved across the two Haemophilus species. Outer core LPS biosynthetic genes are much less prevalent in H. parainfluenzae, although homologues of the H. influenzae LPS genes lpsB, non-phase variable lic2A and lgtC, and losA1, losB1 and lic2C are found in certain isolates. Immunoblotting using antibodies directed against selected LPS epitopes was consistent with these data. We found no evidence for tetranucleotide repeat-mediated phase variation in H. parainfluenzae. Phosphocholine, a phase variable H. influenzae LPS epitope that has been implicated in disease, was absent in H. parainfluenzae LPS as were the respective (lic1) biosynthetic genes. The introduction of the lic1 genes into H. parainfluenzae led to the phase variable incorporation of phosphocholine into its LPS. Differences in LPS structure between Haemophilus species could affect interactions at the bacterial-host interface and therefore the pathogenic potential of these bacteria.
Insights
Lipopolysaccharide (LPS) structures differ between Haemophilus influenzae and H. parainfluenzae, impacting bacterial-host interactions. H. parainfluenzae lacks phosphocholine, a key virulence factor in H. influenzae.
Area of Science:
- Microbiology
- Bacterial Pathogenesis
- Molecular Biology
Background:
- Cell surface lipopolysaccharide (LPS) is a critical virulence factor in Haemophilus influenzae.
- Investigating LPS in the less pathogenic Haemophilus parainfluenzae offers insights into species-specific virulence.
Purpose of the Study:
- To compare the lipopolysaccharide (LPS) biosynthesis genes and structures between Haemophilus influenzae and Haemophilus parainfluenzae.
- To understand the implications of LPS differences on bacterial-host interactions and pathogenic potential.
Main Methods:
- Analysis of 18 commensal H. parainfluenzae isolates for LPS biosynthesis genes.
- Comparison of gene sets with H. influenzae LPS genes.
- Immunoblotting using antibodies against selected LPS epitopes.
- Genetic manipulation to introduce H. influenzae LPS genes into H. parainfluenzae.
Main Results:
- H. parainfluenzae shares inner core LPS biosynthesis genes with H. influenzae but has fewer outer core genes.
- Homologues of specific H. influenzae LPS genes were identified in some H. parainfluenzae isolates.
- No evidence of tetranucleotide repeat-mediated phase variation was found in H. parainfluenzae.
- Phosphocholine, a virulence-associated epitope in H. influenzae, was absent in H. parainfluenzae LPS.
- Introduction of H. influenzae lic1 genes into H. parainfluenzae resulted in phase-variable phosphocholine incorporation.
Conclusions:
- Inner core LPS biosynthesis is largely conserved between H. influenzae and H. parainfluenzae.
- Outer core LPS gene prevalence and structure differ significantly, potentially influencing pathogenicity.
- Absence of phosphocholine in H. parainfluenzae LPS may contribute to its lower virulence compared to H. influenzae.
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