Abstract
BackgroundSialic acid has been shown to be a major virulence determinant in the pathogenesis of otitis media caused by the bacterium Haemophilus influenzae. This study aimed to characterise the expression of genes required for the metabolism of sialic acid and to investigate the role of these genes in virulence.ResultsUsing qRT-PCR, we observed decreased transcriptional activity of genes within a cluster that are required for uptake and catabolism of 5-acetyl neuraminic acid (Neu5Ac), when bacteria were cultured in the presence of the sugar. We show that these uptake and catabolic genes, including a sialic acid regulatory gene (siaR), are highly conserved in the H. influenzae natural population. Mutant strains were constructed for seven of the nine genes and their influence upon LPS sialylation and resistance of the bacteria to the killing effect of normal human serum were assessed. Mutations in the Neu5Ac uptake (TRAP transporter) genes decreased virulence in the chinchilla model of otitis media, but the attenuation was strain dependent. In contrast, mutations in catabolism genes and genes regulating sialic acid metabolism (siaR and crp) did not attenuate virulence.ConclusionThe commensal and pathogenic behaviour of H. influenzae involves LPS sialylation that can be influenced by a complex regulatory interplay of sialometabolism genes.
Highlights
Sialic acid has been shown to be a major virulence determinant in the pathogenesis of otitis media caused by the bacterium Haemophilus influenzae
The genes of the sialometabolism region are conserved in H. influenzae Previous studies by us using a H. influenzae whole genome microarray [25] and by others [12] identified a region of DNA comprising nine contiguous genes that encode functions relating to sialometabolism (Figure 1)
To explore how general this arrangement of the sialometabolism region of DNA is in H. influenzae, we examined 25 NTHi isolates selected because they are epidemiologically distinct and representative of NTHi genetic diversity [17]
Summary
Sialic acid has been shown to be a major virulence determinant in the pathogenesis of otitis media caused by the bacterium Haemophilus influenzae. For Haemophilus influenzae, a Gram-negative bacterium found only in humans, the major surface glycolipid, lipopolysaccharide (LPS), can be sialylated. This bacterium is an obligate commensal of the human respiratory tract but is able to cause significant disease. NTHi LPS plays a role in the complex interactions with the host required in both its commensal and pathogenic behaviours. A role for LPS sialylation in ‘biofilm’ formation has been proposed that may be relevant to both the commensal behaviour and virulence of NTHi [4,6,7]
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