Polysaccharide Component Of Lipopolysaccharide Research Articles

Molecular Basis for Substrate Selectivity and Specificity by an LPS Biosynthetic Enzyme,

Diversity in the polysaccharide component of lipopolysaccharide (LPS) contributes to the persistence and pathogenesis of Gram-negative bacteria. The Nudix hydrolase GDP-mannose mannosyl hydrolase (Gmm) contributes to this diversity by regulating the concentration of mannose in LPS biosynthetic pathways. Here, we present seven high-resolution crystal structures of Gmm from the enteropathogenic E. coli strain O128: the structure of the apo enzyme, the cocrystal structure of Gmm bound to the product Mg2+-GDP, two cocrystal structures of precatalytic and turnover complexes of Gmm-Ca2+-GDP-alpha-d-mannose, and three cocrystal structures of an inactive mutant (His-124 --> Leu) Gmm bound to substrates GDP-alpha-d-mannose, GDP-alpha-d-glucose, and GDP-beta-l-fucose. These crystal structures help explain the molecular basis for substrate specificity and promiscuity and provide a structural framework for reconciling previously determined kinetic parameters. Unexpectedly, these structures reveal concerted changes in the enzyme structure that result in the formation of a catalytically competent active site only in the presence of the substrate/product. These structural views of the enzyme may provide a rationale for the design of inhibitors that target the biosynthesis of LPS by pathogenic bacteria.

The rise and fall of Salmonella Enteritidis in the UK.

After rising in the early 1980s, the number of recorded human cases of Salmonella enterica subsp. enterica in the UK has fallen in the last 5 years, with a particular decline in cases of infection with serovar Enteritidis. This decline has been concomitant with the introduction of vaccination of egg-laying hens against serovar Enteritidis. It is likely that other factors such as improved biosecurity in egg-laying flocks, a build-up of immunity in other animals and the rise in the number of livestock infections with host-adapted serovars of Salmonella have also played a part in this decline. Although human Salmonella cases are currently at their lowest level since 1987, it is important to remember that the reasons for the dominance of Enteritidis in human infection are poorly understood and it is possible that other serovars could share similar properties and the eradication of Enteritidis may leave a niche for them to fill.