title: Relative contributions of lipooligosaccharide inner and outer core modifications to nontypeable Haemophilus influenzae pathogenesis.
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.
authors: Laboratory Microbial Pathogenesis, Fundación Investigación Sanitaria Illes Balears (FISIB), CSIC-Govern de les Illes Balears, Bunyola, Spain.
authors: Pau
authors: P
authors: Morey
authors: Cristina
authors: C
authors: Viadas
authors: Begoña
authors: B
authors: Euba
authors: Derek W
authors: DW
authors: Hood
authors: Montserrat
authors: M
authors: Barberán
authors: Carmen
authors: C
authors: Gil
authors: María Jesús
authors: MJ
authors: Grilló
authors: José Antonio
authors: JA
authors: Bengoechea
authors: Junkal
authors: J
authors: Garmendia
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D018441:Biofilms / Q000254:growth & development; D001996:Bronchopneumonia / Q000382:microbiology / Q000473:pathology; D002448:Cell Adhesion; D004195:Disease Models, Animal; D004731:Endotoxins / Q000378:metabolism*; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D006192:Haemophilus Infections / Q000382:microbiology / Q000473:pathology; D006193:Haemophilus influenzae / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D051379:Mice; D009154:Mutation; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D023181:Antimicrobial Cationic Peptides; D004731:Endotoxins; D008070:Lipopolysaccharides; D037521:Virulence Factors; C023023:lipid-linked oligosaccharides
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