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Background  Sialic 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.    Results  Using 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.    Conclusion  The commensal and pathogenic behaviour of  H. influenzae  involves LPS sialylation that can be influenced by a complex regulatory interplay of sialometabolism genes.

bmc microbiology

Sialic acid mediated transcriptional modulation of a highly conserved sialometabolism gene cluster in Haemophilus influenzae and its effect on virulence