Host-derived sialic acid is incorporated into Haemophilus influenzae lipopolysaccharide and is a major virulence factor in experimental otitis media
Virulence factor
DOI:
10.1073/pnas.1432026100
Publication Date:
2003-07-22T19:39:06Z
AUTHORS (12)
ABSTRACT
Otitis media, a common and often recurrent bacterial infection of childhood, is major reason for physician visits the prescription antimicrobials. Haemophilus influenzae cause approximately 20% episodes otitis but most strains lack capsule, factor known to play critical role in virulence causing invasive H. disease. Here we show that capsule-deficient (nontypeable) strains, sialic acid, terminal residue core sugars lipopolysaccharide (LPS), pathogenesis experimental media chinchillas. We used five epidemiologically distinct isolates, representative genetic diversity inoculate middle ear All animals developed acute persisted up 3 wk, whereas isogenic acid-deficient mutants (disrupted sialyltransferase or CMP-acetylneuraminic acid synthetase genes) were profoundly attenuated. MS analysis indicated WT bacteria lacked any sialylated LPS glycoforms. In contrast, ex vivo organisms recovered from chinchilla exudates was sialylated. conclude glycoforms key pathogenicity nontypeable depend on scavenging essential precursors host during infection.
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