Underlying Glycans Determine the Ability of Sialylated Lipooligosaccharide To Protect Nontypeable Haemophilus influenzae from Serum IgM and Complement Molecular Pathogenesis

Nontypeable Haemophilus influenzae (NTHi) efficiently colonizes the human nasopharynx asymptomatically but also causes respiratory mucosal infections, including otitis media, sinusitis, and bronchitis. The lipooligosaccharide (LOS) on the cell surface of NTHi displays complex glycans that mimic host structures, allowing it to evade immune recognition. However, LOS glycans are also targets of host adaptive and innate responses. To aid in evasion of these responses, LOS structures exhibit interstrain heterogeneity and are also subject to phase variation, the random on/off switching of gene expression, generating intrastrain population diversity. Specific LOS modifications, including terminal sialylation of the LOS, which exploits host-derived sialic acid (Neu5Ac), can also block recognition of NTHi by bactericidal IgM and complement by mechanisms that are not fully understood. We investigated the LOS sialic acid-mediated resistance of NTHi to antibody-directed killing by serum complement. We identified specific LOS structures extending from heptose III that are targets for binding by naturally occurring bactericidal IgM in serum and are protected by sialylation of the LOS. Phase-variable galactosyltransferases encoded by lic2A and lgtC each add a galactose epitope bound by IgM that results in antibody-dependent killing via the classical pathway of complement. NTHi’s survival can be influenced by the expression of phase-variable structures on the LOS that may also depend o...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Molecular Pathogenesis Source Type: research

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Source: International Journal of Environmental Research and Public Health - Category: Environmental Health Authors: Tags: Article Source Type: research
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Source: European Annals of Otorhinolaryngology, Head and Neck Diseases - Category: ENT & OMF Source Type: research
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Source: Veterinary Research - Category: Veterinary Research Source Type: research
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Source: Drugs - Category: Drugs & Pharmacology Source Type: research
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Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
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Source: Genetic Testing and Molecular Biomarkers - Category: Genetics & Stem Cells Authors: Source Type: research
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Source: MicrobiologyOpen - Category: Microbiology Authors: Tags: ORIGINAL RESEARCH Source Type: research
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Source: Journal of Medical Microbiology - Category: Microbiology Authors: Tags: J Med Microbiol Source Type: research
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