You are here: Home Published Research Relative contribution of lipooligosaccharide inner and outer core modifications to nontypable Haemophilus influenzae pathogenesis.

Pau Morey, Cristina Viadas, Begoña Euba, Derek W Hood, Montserrat Barberán, Carmen Gil, María J Grilló, José A Bengoechea, and Junkal Garmendia (2013)

Relative contribution of lipooligosaccharide inner and outer core modifications to nontypable Haemophilus influenzae pathogenesis.

Infection and immunity.

Nontypable 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 contribution of NTHi LOS modifications to virulence properties of the bacterium has not been comprehensively addressed. Using NTHi strain 375, an isolate where the detailed LOS structure has been determined, we compared systematically a set of isogenic mutant strains expressing sequentially truncated LOS. The relative contribution of 2-keto-3-deoxyoctulosonic acid, the tri-heptose inner core, oligosaccharide extensions on heptoses I and III, phosphorylcholine, di-galactose and sialic acid to NTHi resistance to antimicrobial peptides (AMP), self-aggregation, biofilm formation, cultured human respiratory epithelial infection, and murine pulmonary infection was 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; opsX, lgtF and lpsA contribute to lung infection. Depending on the phenotype, the involvement of these LOS modifications occurs at a different extent, independently or having an additive effect in combination. Collectively, we propose the relative contribution of LOS epitopes to NTHi virulence and frame a range of pathogenic traits in the context of infection.

 
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