Relative contributions of lipooligosaccharide inner and outer core modifications to nontypeable Haemophilus influenzae pathogenesis

Pau Morey, Cristina Viadas, Begoña Euba, Derek W Hood, Montserrat Barberán, Carmen Gil, María Jesús Grilló, José Antonio Bengoechea, Junkal Garmendia

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Nontypeable Haemophilus influenzae (NTHi) is a frequent commensal of the human nasopharynx that causes opportunistic infection in immunocompromised individuals. Existing evidence associates lipooligosaccharide (LOS) with disease, but the specific and relative contributions of NTHi LOS modifications to virulence properties of the bacterium have not been comprehensively addressed. Using NTHi strain 375, an isolate for which the detailed LOS structure has been determined, we compared systematically a set of isogenic mutant strains expressing sequentially truncated LOS. The relative contributions of 2-keto-3-deoxyoctulosonic acid, the triheptose inner core, oligosaccharide extensions on heptoses I and III, phosphorylcholine, digalactose, and sialic acid to NTHi resistance to antimicrobial peptides (AMP), self-aggregation, biofilm formation, cultured human respiratory epithelial infection, and murine pulmonary infection were assessed. We show that opsX, lgtF, lpsA, lic1, and lic2A contribute to bacterial resistance to AMP; lic1 is related to NTHi self-aggregation; lgtF, lic1, and siaB are involved in biofilm growth; opsX and lgtF participate in epithelial infection; and opsX, lgtF, and lpsA contribute to lung infection. Depending on the phenotype, the involvement of these LOS modifications occurs at different extents, independently or having an additive effect in combination. We discuss the relative contribution of LOS epitopes to NTHi virulence and frame a range of pathogenic traits in the context of infection.

Original languageEnglish
Pages (from-to)4100-11
Number of pages12
JournalInfection and Immunity
Volume81
Issue number11
DOIs
Publication statusPublished - Nov 2013

Keywords

  • Animals
  • Antimicrobial Cationic Peptides
  • Biofilms
  • Bronchopneumonia
  • Cell Adhesion
  • Disease Models, Animal
  • Endotoxins
  • Epithelial Cells
  • Female
  • Haemophilus Infections
  • Haemophilus influenzae
  • Humans
  • Lipopolysaccharides
  • Metabolic Networks and Pathways
  • Mice
  • Mutation
  • Virulence
  • Virulence Factors

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