Evolution and Biology of Sialic Acids

We used approaches in genomics and phylogenetics together with targeted biochemical validation to make predictions of carbohydrate structure (i.e. type of NulO) based on genomic sequences. This approach revealed that biosynthesis of NulOs was far more common than previously realized.

Phylogenetic analysis of NulO pathways revealed that sialic acids (depicted in red clades in the figure to the right) were 'invented' independently at least 3 times by bacteria. Multiple lines of evidence suggest that one of these inventions may have involved adaptation of a bacterial pathway for legionaminic acid synthesis (clade shown in green), a NulO molecule with the same stereochemistry as sialic acid.

This approach also revealed new potential examples of sialic acid mimicry among bacterial pathogens, a known virulence factor in other contexts that enables pathogens to cause both localized and systemic infections.

 V. vulnificus gastroenteritis occurs most commonly after consumption of contaminated raw oysters and can lead to septicemia with a 50-80% fatality rate. 

We have shown that V. vulnificus, among many other species of the genera Vibrionacea, expresses sialic acid-like molecules. We found that Lineage I and Lineage II isolates, which are mostly clinical and environmental isolates respectively, encode lineage-specific alleles of the biosynthetic pathway for these sugars. Moreover, Lineage I isolates of mostly clinical origin have on average 40X higher density of expression of these molecules on their surface compared to Lineage II isolates of mostly environmental origin. A high density of sialic acid-like sugars on V. vulnificus may be significant during bloodstream infection by allowing the bacterium to evade innate immune responses.